oEPA
United States
Environmental Protection
Agency
National Institute of
Environmental Health Sciences
Pediatric Environmental
Health Specialty Units
Proceedings of the 2007 Children's
Environmental Health Workshop:
Discover, Treat, Prevent, Prepare
OCTOBER 10-13,2007
THE HAMILTON HOTEL
14TH AND K STREETS, NW
WASHINGTON, DC 20005
[ National Center for Environmental Research
I Science To Achieve Results (STAR) Research Program
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2007 Children's Environmental Health Workshop:
Discover, Treat, Prevent, Prepare
Hamilton Crowne Plaza
1001 14th Street, NW
Washington, DC
October 11-12, 2007
Agenda
Purpose:
This workshop brings together the expertise and experience of the Pediatric Environmental Health Specialty
Units (PEHSU) of North America and the Children's Environmental Health Centers to explore the latest
research findings and their practical application in community settings. This workshop is sponsored by the
U.S. Environmental Protection Agency (EPA) (Office of Research and Development and Office of Children's
Health Protection and Environmental Education), the Department of Health and Human Services (Agency for
Toxic Substances and Disease Registry of the Centers for Disease Control and Prevention and the National
Institute of Environmental Health Sciences), and the Association of Occupational and Environmental Clinics
in recognition of 10 years of federal effort to protect children's environmental health as called for in Executive
Order 13045, Protection of Children from Environmental Health Risks and Safety Risks.
This anniversary provides the children's environmental health community with an opportunity to reflect on the
progress that has been made and to formulate our vision for the future of children's environmental health.
7:30-8:15a.m.
8:15-9:00 a.m.
Thursday, October 11, 2007
Breakfast and Registration
Welcome/Review of Agenda
William H. Sanders III, Dr.P.H.
Director, National Center for Environmental Research, EPA
Dona DeLeon, Acting Director, Office of Children's Health Protection and Environmental
Education, EPA
Kevin Y. Teichman, Ph.D.
Acting Deputy Assistant Administrator for Science, EPA
Children's Environmental Health: Looking Backward, Looking Forward
Howard Frumkin, M.D., Dr.P.H., M.P.H.
Director, National Center for Environmental Health, Agency for Toxic Substances and
Disease Registry, Centers for Disease Control and Prevention
Gwen Collman, Ph.D., Chief, Susceptibility and Population Health Branch, Division of
Extramural Research and Training, National Institute for Environmental Health Sciences
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9:00 - 10:45 a.m. Session I: Evolution of Biomarkers for Pesticides: Examples From the
Agricultural Setting
Co-Chairs: Catherine Karr, M.D., Ph.D., Director, Northwest PEHSU
Elaine Faustman, Ph.D., Director, Center for Child Environmental
Health Risks Research
In the late 1990s, an epidemic of initially unrecognized organophosphate (OP)
poisoning affecting families in eight states helped motivate the development of the
PEHSU network to increase the capacity of physicians to identify and prevent
adverse effects of environmental toxicants. In recent years, concern has focused on
the potential child health implications from chronic, lower level exposure and are a
focus of ongoing longitudinal birth cohort studies and exposure pathway studies
within the EPA/NIEHS Children's Centers Program. An accumulating evidence base
led to recent restrictions in residential use of these products; however,
organophosphate insecticides continue to have extensive use in many agricultural
settings.
In research and clinical settings, biomarkers of organophosphate exposure, toxicity,
and susceptibility have contributed to improved understanding of exposure pathways
and adverse health outcomes. The session will discuss: (a) use of pesticide
metabolite concentrations to estimate exposure type, extent, and source attribution
based on EPA/NIEHS-sponsored studies and CDC population surveillance; (b)
strengths and pitfalls regarding the determination of cholinesterase enzyme activity
in clinical practice, occupational surveillance, and research as a marker of OP
toxicity; and (c) evolving insight into the importance of gene-environment interaction
in OP toxicity using recent findings based on paraoxonase 1 studies in the
Children's Centers.
The key areas for discussion will include the current stage of validation of these OP-
related biomarkers and critical missing data/applications to consider in moving the
translation of each biomarker forward for clinical and public health relevance. The
links between research, education, and risk communication activities from PEHSU
and the Children's Centers will be highlighted.
Presenters:
Elaine Faustman, Ph.D.
Catherine Karr, M.D., Ph.D.
Kim Harley, Ph.D., University of California at Berkeley, Center
for Children's Environmental Health Research
John Furman, Washington State Department of Labor and Industries
Bill Griffith, Ph.D., Center for Child Environmental Health Risks Research
Frederica Perera, Dr.PH, Columbia Center for Children's Environmental
Health
10:45-11:00 a.m. Break
11:00 a.m. - 12:45 p.m. Session II: Phthalates Exposure in Childhood: Is There Evidence of Harm?
Chair: Maida P. Galvez, M.D., M.P.H., Mount Sinai PEHSU, and Mount
Sinai Center for Inner City Toxics and Children's Health
Phthalates are chemicals added to plastics that impart flexibility and act as a scent
stabilizer for a wide range of products—from food packaging and children's toys to
personal hygiene products such as shampoos, fragrances, and nail polish.
Concerns exist about the potential for phthalates to act as endocrine disrupters,
largely based on animal studies and a small but growing body of evidence in human
studies.
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Several countries around the world, beginning with the European Union, have
subsequently banned phthalates in children's products. Since then, widespread
media reports on the potential harms of toxic toys and other children's products
containing phthalates have raised parental anxiety about the impact of
environmental exposures on their children.
Primary care pediatricians are subsequently faced with clinical questions that are
often difficult to answer given the limited medical school training in children's
environmental health, particularly in newly emerging exposures of concern such as
phthalates.
This session will present clinical scenarios commonly encountered by general
pediatricians and PEHSUs regarding questions about phthalates. The goal of this
session is to describe: (a) exposure levels in pregnant women, toddlers, and
school-aged children; (b) sources of exposure; and (c) known and potential health
outcomes. Data will be shared from three cohorts: A cohort of pregnant women in
New York (Dr. Robin Whyatt, Columbia University Center for Children's
Environmental Health); a cohort of 6 to 24-month-old infants from California,
Minnesota, and Missouri (Dr. Sheela Sathyanarayana, University of Washington,
Seattle, Northwest PEHSU); and a cohort of 6 to 8-year-old New York City
children (Drs. Mary Wolff and Maida Galvez, Mount Sinai Center for Children's
Environmental Health and Mount Sinai PEHSU).
Key areas for discussion will include: (1) What is the current evidence for adverse
health outcomes? (2) What are the research gaps? (3) What health messages on
phthalates can we share with families now? (4) What policy issues remain
unresolved?
Presenters: Maida P. Galvez, M.D., M.P.H., Mount Sinai PEHSU, and Mount
Sinai Center for Inner City Toxics and Children's Health
Robin Whyatt, Dr.P.H., Deputy Director, Columbia Center for
Children's Environmental Health
Sheela Sathyanarayana, M.D., Northwest PEHSU
Mary Wolff, Ph.D., Director, Mount Sinai Center for Inner City Toxics
and Children's Health
12:45-2:00 p.m. Lunch (on your own)
2:00 - 3:15 p.m. Session III: The Evolving Science and Practice of Environmental Management
for Asthma Prevention and Care
Co-Chairs: Kimberly Gray, Ph.D., National Institute of Environmental Health
Sciences
Ley/a E. McCurdy, National Environmental Education Foundation
Asthma is a chronic respiratory disease characterized by episodes of inflammation
and narrowing of small airways. Childhood asthma, in particular, continues to be a
major, vexing public health problem in the United States. Low-income populations,
minorities, and children living in inner cities still experience disproportionately higher
morbidity and mortality due to asthma. Asthma's effects on children and
adolescents account for millions of lost days of school missed annually and cost
more than $3 billion per year to treat. According to the Centers for Disease Control
and Prevention in 2005, prevalence rates for childhood asthma peaked at 8.9
percent; more than 6 million of the nation's children. Even so, there have been
important gains recently, including a reduction in childhood deaths from asthma
attacks, a leveling of hospitalizations, improved patient education, and evidence of
earlier clinical recognition and treatment.
Currently, there are neither known preventions nor cures for asthma. However,
avoiding environmental agents that promote or exacerbate asthma attacks is one of
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the primary goals of good asthma management. Considerable research within the
EPA/NIEHS Children's Centers has primarily focused on four areas: (1) household
interventions and avoidance of environmental triggers, (2) exposure and effects of
air pollution, (3) gene-environment interactions, and (4) mechanisms of early
immune deregulation and subsequent asthma risk.
This session will: (1) review potential mechanisms (immune, epigenetic) for the
effects of prenatal and early postnatal exposure on asthma outcomes, and the
ongoing mechanistic work being performed by the Children's Centers; and (2)
highlight currently recommended household environmental management strategies
most useful for clinical settings based on the 3rd Expert Panel Report of Guidelines
on Asthma issued August 2007.
The discussion will broaden to include recent research findings of Children's
Centers, including the impact of chronic exposure to air pollution and the
contribution of genetic vulnerabilities in an open-session format.
Presenters: David Rowson, Office of Air and Radiation, EPA
Rachel Miller, M.D., FAAAAI, Columbia Center for Children's
Environmental Health
Discussant: Elizabeth Matsui, M.D., M.H.S., Center for Childhood Asthma in
the Urban Environment
James M. Seltzer, M.D., University of California, PEHSU
3:15-3:30 p.m. Break
3:30 - 5:15 p.m. Session IV: Early Life Exposures to Metals and Neurotoxic Outcomes
Co-Chairs: Isaac Pessah, Ph.D., Director, University of California at Davis,
Center for Children's Environmental Health
Nigel A. Fields, M.S.P.M., National Center for Environmental
Research, EPA
There has been significant public health progress in reducing chronic high level
exposures to metals, such as lead and mercury, which can cause neurological
damage at any age. For instance, today most children in the United States maintain
average blood lead levels well below the action level of 10 ug/dL. This has been
accomplished largely through state and local education and advisories, multimedia
public health campaigns, and federal regulation. However, there is increasing
evidence that early life exposures to toxic metals, particularly during fetal
development, may contribute to behavioral effects and adversely affect cognitive
functioning well into adult life. There also is growing concern regarding the social
context of exposure, or non-chemical stressors, which may modify the uptake and
neurotoxic effect of metals such as lead, mercury, and manganese, both pre- and
post-natally. Yet, currently there is limited ability to identify and translate clinically
significant prenatal biomarkers of exposure, susceptibility, and effect that could
better elucidate risks of metal exposures during pregnancy.
The purpose of this session is to: highlight recent findings of the long-term effects of
metals and metal mixtures; discuss the utility of perinatal biomarkers of lead and
mercury; and consider modifying factors that might offer additional protection or
confer additional risk to children. Based on three longitudinal cohorts and one case-
control study, this session will explore: (1) the plausible interactive effects of metals
and psychosocial stresses on neurodevelopment; (2) the use of new mercury
exposure biomarkers and epidemiological approaches in autism etiology research;
(3) the long-term behavioral consequences of fetal and childhood exposures to lead,
resulting in criminality and increased societal risks; (4) the impact of early exposure
to lead on adult cerebral cortical anatomy and function as revealed by advanced
neuro-imaging techniques; and (5) the interactive effects of exposure to multiple
metals on neurodevelopment.
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Panel and Audience Discussion Questions: What are the key window periods of
concern for fetal exposure to metals? What factors confer added protection or
increased risk from early life exposures to metals? How should the long-term effects
of metal exposures inform public health actions during early childhood
development?
Presenters: Irva Hertz Piciotto, Ph.D., Deputy Director, University of California
at Davis, Center for Children's Environmental Health
Robert Wright, M.D., New England PEHSU and Harvard Center for Metal
Mixtures and Children's Health
Kim Dietrich, Ph.D., Cincinnati Children's Environmental Health
Center
5:30 p.m. Reception and 3rd Annual EPA Children's Environmental Health Excellence
Award Ceremony (Open Invitation)
Dr. William H. Sanders III, Presiding
The Children's Environmental Health Excellence
Awards recognize ongoing and sustainable
dedication to, and notable leadership in,
protecting children from environmental health
risks at the local, regional, national, and
international level. Excellence Awards are
presented to groups or individuals that exemplify
invaluable leadership in the protection of children
from environmental health risks. There are 10
winners in 2007, 7 in the health care provider
category, 1 for schools, 1 for corporate
leadership, and 1 for research.
The Children's Environmental Health Champion is an honorary award presented to
individuals to recognize their outstanding efforts and commitment to advancing
environmental health issues. The 2006 Children's Environmental Health Champion
award was presented to Philip J. Landrigan, M.D., M.Sc., and in 2005 our Champion
Award winner was Ramona Trovato.
Who will it be for 2007? Join us and find out!
Friday, October 12, 2007
7:30 a.m. Breakfast
8:30 - 9:30 a.m. Session V: Transportation, the Built Environment, and Children's Health
Moderator: Joanne Rodman, Acting Director, Child and Aging Health
Protection Division, OCHPEE
This session will explore trends in population demographics, how and where
development occurs, the explosive growth in international trade, and the anticipated
impacts on public health, the environment, transportation, and infrastructure
planning. There will be a more detailed look at trends in school siting with
relationship to roadways and other factors and discussion of the implications of
those trends on efforts to develop healthy communities. The session will examine
how a school's site and its context within a community can affect children's health,
as well as the environment, economic development, land use, and transportation.
Recent studies on proximity to traffic and adverse health effects will be discussed,
as well the health and community impacts of port and "goods movement" (freight
transportation) expansion in many U.S. cities. Possible points of intervention for the
public health community on this issue also will be discussed.
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Tim Torma, EPA, Office of Policy, Economics and Innovation
Andrea M. Hricko, M.P.H., University of Southern California, Center for
Children's Environmental Health
9:30 - 10:00 a.m. The National Children's Study: Opportunities for Adjunct Studies
Marion Balsam, M.D., Research Partnerships Program Director, National Children's
Study
As the National Children's Study proceeds, scientific knowledge will evolve and the
Study will serve as an appropriate platform on which to build additional scientific
studies. Investigators from various sectors will propose adjunct studies. Such
studies will enhance the breadth, depth, and value of the Study and will assure
continued interest of a diverse group of investigators, which is critical to the overall
success of the Study.
An adjunct study involves a portion of the National Children's Study cohort, utilizing
individually or in combination, any of the following: The Study participants, their bio-
specimens, or their environmental samples. Adjunct studies can take place at one
or more Study Centers, on all or a portion of their Center participants. Adjunct
studies generally will be initiated and planned outside of the Study protocol planning
process and funded with non-Study funding; that is, by such mechanisms as
government grants (for example, R01) applied for by the initiator, by intramural
federal resources, through public private partnerships, or from other sources. To
preserve the quality and integrity of the National Children's Study, all proposals for
adjunct studies will receive rigorous review. This presentation will include a brief
overview of adjunct studies and of the review and approval process.
10:00-10:15 a.m. Break
10:15-11:15 a.m. Session VI: Children's Protection in the Aftermath of a Natural Disaster:
Tools for Recovery and Communicating Risks
Chair: Debra Cherry, M.D., M.S., University of Texas Health Center at
Tyler, Southwest PEHSU
Hurricane Katrina, which struck the Gulf Coast on August 29, 2005, has been called
the most devastating natural environmental calamity in U.S. history. More than
354,000 homes along the Gulf Coast were destroyed or damaged beyond repair.
Katrina damaged more than 200 sewage treatment plants and 140 oil and gas
platforms and leached hazardous chemicals and fuels from hundreds of small
businesses as the floodwaters passed over them. Rampant mold growth, mountains
of debris, and widespread cleanup, demolition, and construction projects followed.
Some residents were housed "temporarily" in FEMA trailers with hastily assembled
indoor materials that off gassed high levels of formaldehyde. Many New Orleans
residents left the area permanently.
This session will describe some of the efforts of a Gulf Coast pediatrician, NIEHS
scientists, and PEHSU clinicians to respond to this calamity. Dr. Scott Needle
(pediatrician, relocated from Bay St. Louis, Mississippi to Florida) will describe via
Web conference his experience on the front lines of the disaster, the disaster
preparedness document he prepared on behalf of AAP, and his federal testimony on
the health effects of formaldehyde in FEMA trailers. Dr. Marie Lynn Miranda
(scientist and CIS expert, Duke University) will describe the NIEHS Hurricane
Response Portal, a research and planning tool for the Gulf Coast, which overlays
multiple geographic and demographic features, such as location of hazardous waste
sites, racial composition, and extent of flooding. Dr. Debra Cherry (occupational
medicine physician from the Southwest PEHSU) will briefly present fact sheets on
sludge, formaldehyde, and mold, as well as the PEHSU/AAP guidelines for returning
children to previously flooded areas.
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Key areas for discussion will include: (1) How should federal agencies communicate
with local clinicians in the aftermath of a natural disaster? (2) What types of tools
are most useful? (3) What environmental health risks were overblown, and which
were understated in the aftermath of Hurricanes Katrina and Rita?
Presenters: Debra Cherry, M.D., M.S., University of Texas Health Center at
Tyler, Southwest PEHSU
Marie Lynn Miranda, Ph.D., Director, Duke University Southern
Center for Environmentally-Driven Disparities in Birth Outcomes
Scott Needle, M.D., Pediatrician, formally of Bay St. Louis, MS
11:15 a.m. - 12:15 p.m. The National Forum on Children and Nature
Key Note Address: Lawrence A. Selzer, President and Chief Executive Officer,
Conservation Fund
Introduction and Discussant: HowardFrumkin, M.D., Dr.P.H., M.P.H.
Launched in June 2007, the National Forum on Children and Nature will involve
governors, mayors, corporate CEOs, heads of environmental organizations, and
leaders from health and education institutions, and will invest several million dollars in
projects with on-the-ground tangible results that address the issue of children's
isolation from nature. The Forum will identify 20 nationally significant demonstration
projects in four key areas of health, education, the built environment, and
media/culture that, individually and collectively, will provide substantial steps toward
improved children's health and environmental stewardship.
12:15 - 12:30 p.m. Closing Remarks: Dr. William H. Sanders III, EPA
Acknowledgments
Many thanks to the honorary workshop co-chairs: William Sanders and Howard Frumkin
Also special thanks to the workshop planning committee: Nora Conlon, Elaine Faustman, Maida Galvez,
Kimberly Gray, Michael Hatcher, Catherine Karr, Leyla McCurdy, Ketna Mistry, Jerome Paulson, Isaac Pessah, and
Maryann Suero
And thanks to the Washington, DC, coordinating team: Martha Berger, Richard Callan, Cerena Cantrell, Tina
Conley, Paula Davis, Nigel Fields, Bettina Fletcher, Carolyn Hubbard, and Susie Warner
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2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
2007 Children's Environmental Health Workshop:
Discover, Treat, Prevent, Prepare
Hamilton Crowne Plaza
1001 14th Street, NW
Washington, DC
October 11-12, 2007
MEETING SUMMARY
OCTOBER 11,2007
INTRODUCTION AND OVERVIEW
The U.S. Environmental Protection Agency (EPA) 2007 Children's Environmental Health Workshop:
Discover, Treat, Prevent, Prepare was held on October 11-12, 2007, in Washington, DC. The workshop
brought together a diverse group of clinicians, researchers, and health advocates from academic, gov-
ernment, and nonprofit organizations. Participants discussed issues in clinical practice, ongoing research
in children's environmental health, and opportunities for translating scientific findings. The workshop
also served as a stimulus for increased collaborations among the Pediatric Environmental Health
Specialty Units (PEHSUs) and the Centers for Children's Environmental Health and Disease Prevention
Research. Approximately 133 individuals attended.
Welcome and Review of the Agenda
Nigel Fields, William H. Sanders, III, Dona DeLeon, and Kevin Y. Teichman, U.S. EPA; Paula
Davis, Association of Occupational and Environmental Clinics (AOEC)
Mr. Fields thanked attendees for their participation. He noted that the 10th anniversary of Executive
Order 13045, Protection of Children from Environmental Health Risks and Safety Risks, was an
opportune time to celebrate the progress made in children's environmental health (CEH) and to align
perspectives for the future of this field. He invited participants to engage workshop speakers in their
discussions about how to further CEH protection.
Ms. Davis, Coordinator of the Pediatric Environmental Health Specialty Units Program (PEHSU) wel-
comed presenters and workshop participants. She expressed her interest in collaborating with PEHSU
colleagues and other scientists involved in CEH to help bridge the gap between research and practice.
Before his recent appointment as Director of the National Center for Environmental Research (NCER),
Dr. Sanders previously worked directly with the PEHSUs and indirectly with the Children's Environ-
mental Health Centers (CEHC) in his role as Acting Director of the Office of Children's Health
Protection and Environmental Education. He noted the variety of constituents in attendance and remarked
that it is a great opportunity for bringing together representatives from the PEHSUs with the CEHC
Directors in a central venue. He presented an overview of the workshop agenda, explaining the nature of
each session. Dr. Sanders also invited participants to attend the Third Annual Excellence Awards
Ceremony at end of the first day.
Ms. DeLeon explained that she is new to the Office of Children's Health Protection and Environmental
Education but has spent many years at EPA, including working with and examining the delivery system at
The Office of Research and Development's National Center for Environmental Research
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2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
the state and local levels. Implementation of environmental policy is taking place at the local level; how
regulation implementation is translated at the local level and communicated to the public is critical to
keep environmental progress moving forward. This audience plays an important role in communicating
health risks and promoting the science that underlies decision-making to the public working with families
and children. She congratulated attendees for the progress that has been made and thanked them for their
continuation of these efforts. She welcomed the international visitors and commented that she looks
forward to learning more about children's environmental health issues and how EPA can assist
researchers in advancing these issues.
Dr. Teichman welcomed participants and remarked that the CEH protection community experienced
another tremendous year of growth; he noted that it was appropriate that the workshop was held during
Children's Health Month. He also welcomed Dr. William Sanders to EPA's Office of Research and
Development (ORD) and expressed his gratitude to the Center for Children's Environmental Health and
Disease Prevention Research; the National Institute of Environmental Health Sciences (NIEHS);
PEHSUs; the Agency for Toxic Substances and Disease Registry (ATSDR); AOEC; and the new health
care provider capacity-building grantees and Children's Environmental Health Champion Award winners.
The mission of EPA is to protect human health and the environment. In attempting to achieve this goal,
the Agency is examining one of the most vulnerable populations with increased specificity. There is a
wide range of genetic susceptibility among newborns and young children to exposure from household or
agricultural pesticides. Where a child lives within the urban environment may significantly influence or
impact his or her exposures and health outcomes. With the passing of several federal mandates, EPA has
emphasized the identification of child-specific exposures, health risks, and protective actions for more
than a decade. Within ORD, these mandates have stimulated a wide array of research activities, with the
purposes of studying how chemical exposures change across life stages; gaining a greater understanding
about the genetic factors that contribute to children's vulnerability to air pollution, pesticide exposures,
and heavy metals; validating novel methods for both aggregate and cumulative exposures to single and
multiple chemical, biological, and radiological agents; discovering, translating, and employing
biomarkers of exposure effect and susceptibility; and promoting cost-effective sustainable household- and
community-level interventions.
EPA scientists and their academic partners have applied their expertise to these efforts because children
may be at increased risk from environmental influences as a result of their vulnerable developing systems
and enhanced exposures to many agents. These environmental influences include the quality of air,
ingested lead, and exposures to chemicals and mold; all of these factors are within society's power to
control. ORD researchers have contributed to improving CEH in many ways. The Stochastic Human
Exposure and Dose Simulation Multiscale Model is now used as a primary tool for simulating exposures
to a variety of chemicals that enter the body to determine how best to advise the public on reducing
children's exposures to toxic compounds. During the past 10 years, EPA has improved the ability to
monitor chemical exposures and assess the effects based on the development, validation, and imple-
mentation of biological markers. EPA scientists and those supported by the Agency are leading efforts to
validate noninvasive biomarkers and to apply them in epidemiologic studies and clinical settings. ORD
also is contributing to the Agency's next Report on the Environment by developing the scientific basis for
the use of health outcomes to measure and evaluate environmental policy decisions.
ORD is only one contributor to improving the understanding of CEH; community partners play a critical
role in informing, implementing, and translating research findings. Workshop participants have the
opportunity to discuss findings and clinical experiences and translate those experiences for advancing
more protective medical guidance in environmental policy into the future. Today's sessions, which focus
on the translation of research and clinical insights regarding organophosphates (OPs), phthalates, asthma,
and exposures to metals, will specifically concentrate on prenatal and early life exposures and the
2
The Office of Research and Development's National Center for Environmental Research
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2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
subsequent health effects associated with these exposures. The next day's sessions will examine what lies
ahead for researchers, clinicians, and health advocates as increasingly complex public health challenges
that also will impact children's health emerge. These challenges include persistently high rates of low
birth weight and preterm births; increasing rates of neurobehavioral disorders in young children, such as
autism and attention deficit hyperactivity disorder (ADHD); increasing body burdens of potentially
endocrine-disrupting compounds; escalating prevalence rates for obesity and type II diabetes; growing
disparities between low-income and minority groups to chemical exposures; the risks of climate change;
the emergence and application of nanotechnology; and complex trends in urbanization. EPA will need
partners in determining the environmental factors and related health outcomes of these issues.
ORD will continue to work closely with the Centers for Disease Control and Prevention (CDC), National
Institutes of Health (NIH), and international collaborators such as the World Health Organization (WHO)
to systematically discover ways to protect children in a rapidly evolving world. The National Children's
Study (NCS) holds much promise for gaining a deeper understanding of these complex issues and to
make better, more targeted decisions for promoting healthier environments. The NCS represents a truly
unprecedented collaboration among government agencies, private industry and foundations, community
leaders, and university-based scientists around the nation devoted to improving children's health. EPA
conducted and supported much of the science that laid the foundation for this ambitious study.
Researchers from the CEHCs participated in workgroups that developed the core hypotheses for the
studies, and the Centers also collectively published "Lessons Learned" papers to offer guidance to the
NCS for practical approaches to sustaining long-term studies and interpreting complex data.
Last week, EPA joined the National Institute of Child Health and Development (NICHD) in announcing
the 22 Health Study Center awards, which joined the previously awarded Vanguard Centers in officially
launching the study next year. As the research community moves forward to build on the past decade of
success, it is clear that meeting these challenges will require strong, committed partnerships that better
link research questions, health care practice, and environmental health.
Children's Environmental Health: Looking Backward, Looking Forward
Howard Frumkin, CDC, and Gwen Collman, NIEHS
In 1993, the National Academy of Sciences published Pesticides in the Diets of Infants and Children.
This report helped establish the scientific basis for the CEH movement. Executive Order 13045 is a
milestone in the movement, but since its enactment, the world has changed in many ways. For instance,
10 years ago, people did not routinely discuss the enhanced vulnerability of children, and preparedness
was not a commonly used term in the public health world. Much work has been accomplished in the CEH
field during the past 10 years in the areas of research, education, and service. Disease-specific research,
community-based participatory research, research on the combination of genetic and environmental
factors, and studies on vulnerable populations have expanded. Education has been extended to include
fellowship training, and the field has seen an increase in the publication of books, papers, and Web sites
related to CEH. The development of community networks, PEHSUs, and technical tools have added to
the list of services that the scientific community provides to the public, but it is time to evaluate these
accomplishments by asking what they have achieved in terms of improving children's health. Are
children healthier now? Do health care providers and parents know how to provide children with safe and
wholesome environments more effectively than they did 10 years ago? Has there been a continuing record
of policy-making reflecting the importance of CEH?
This month, October 2007, marks the 10th anniversary of the Executive Order, and the CEH community
is entering a new decade with the chance to reinvent, reinvigorate, and re-expand efforts and move from
an individual clinical approach to a more encompassing legacy approach of caring for future generations.
Biomonitoring is a well-established tool for determining known toxicants in the bodies of children. This
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2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
tool will be instrumental in focusing future research trends by measuring decreases in current chemicals
of concern and identifying possible emerging toxicants. Genetic science will transform the field as
research continues and scientists deepen their understanding of gene-environment interactions. In
addition, there appears to be a change in the political climate that is more sympathetic to CEH. The child
health community must take advantage of these advances to confront current and future challenges.
Challenges during the next 10 years include poverty, changing chemical toxicity, dealing with the built
environment, climate change, mental health burdens, and communication.
Poverty and lack of insurance are two of the most important threats to children's health, as underscored
by the American Cancer Society's 2007 public relations theme, "Access to Health Care." The built
environment has impacted children's health by engineering physical activity out of neighborhoods and
communities. Children and adults now must drive to most destinations, including grocery stores,
pharmacies, shopping malls, and schools. Low physical activity has been linked to childhood obesity and
an increase in diabetes, and the increase in vehicle traffic is adding to environmental pollution. The built
environment also discourages childrens from spending time outside. The author of Last Child in the
Woods advocates "saving our kids from nature-deficit disorder" and maintains that spending time in
natural settings is an important part of a healthy childhood. One of the mechanisms of the benefits of
nature contact seems to be through attention-restoration theory, which states that attention is focused and
distractions are minimized when children have the chance to be outside. This book has given rise to some
very interesting efforts. The Children and Nature Network links people working to promote initiatives at
the state level, including the "Leave No Child Inside" initiative. A number of federal agencies, such as the
U.S. Fish and Wildlife Service, have developed programs about reconnecting children and nature. An
initiative called "The National Forum on Children and Nature" seeks to support 20 nationally significant
demonstration projects across the country that will restore kids into national settings, with a focus on
underserved and minority children. Research on the health evidence of these initiatives should be part of
the CEH portfolio.
Climate change is an important and growing environmental health concern. In addition to potential
physical effects, children now face potential psychological effects, including some effects that may stem
from the fear associated with global warming. Other psychological effects already have been seen in the
aftermath of recent hurricanes, which are predicted to become more severe with global warming. This
kind of message in the media is becoming more common now, with rather apocalyptic narratives about
climate change. Journalistic accounts of schools have described evidence of terror in children about the
world and what it has in store for them. This must be considered because climate change is an issue that is
going to remain for a long time. The manner in which it is discussed either will scare and immobilize
people, or it will spur them to constructive action; the right message must be promoted. The reactions of
adults influence children's reactions. Aftereffects of climate-related events must be considered as well;
the biggest health burden of Hurricane Katrina, in retrospect, is the mental health burden. The anticipation
of bad things happening, the aftermath, and the post-traumatic phase are serious mental health concerns
that threaten children, and this needs to be part of CEH thinking.
"The Death of Environmentalism," an essay by Ted Nordhaus and Michael Shellenberger, was considered
a "big picture" piece on environmentalism. It challenged some of the basic assumptions of contemporary
environmentalism. The book-length expansion of that essay, Breakthrough, is provocative reading, and
some of its points are very relevant to children's environmental health. Many CEH messages are negative:
stopping the bad rather than creating the good. The authors recommend articulating a positive, compelling
image of a healthy, wholesome world, rather than focusing so much on the negative. Positive messages
are compelling and motivating to the public. Additionally, the challenge of climate change is so massive,
global, and complex that it can only be overcome if the issue categories of the past are discarded and an
aspirational vision of the future is embraced. According to the authors, environmentalists should think
about job creation, economic development, law enforcement, and other important issues traditionally
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outside the environmental arena. A similar approach may well be advisable for CEH. In communities
where toxic exposures for children are a concern, poor education, joblessness, or squalor in the physical
environment often are more important problems than the toxic exposures. The more globally children's
problems can be addressed, the better they will be managed; broad thinking and getting outside of
traditional categories can be beneficial. Climate change calls for expanded thinking.
One method by which CEH research portfolios can be expanded is to leverage opportunities with other
partners, such as the U.S. Fish and Wildlife Service, which is actively involved in getting children back
into the outdoors; the U.S. Department of Housing and Urban Development (HUD), which attempts to
improve the quality of housing; and the U.S. Department of Education, which is concerned with healthy
schools. Leveraging of opportunities and development of new partnerships must be creative, as concerns
increase without increasing resources.
Dr. Collman explained that NIEHS has a strong portfolio in research areas that are now classically part of
the rubric of CEH, such as basic mechanisms of toxicity during development, early life, and in organ
systems related to diseases. The executive orders, reports, and regulations provided an impetus for
moving the science forward and moving individual scientific inquiries in individual laboratories to
partners across a spectrum of science. These efforts were furthered by the creation of the CEHCs, which
bring together scientists of different disciplines to work with local health advocates and community
partners. Through multidisciplinary research and outreach projects, the Centers are investigating
environmental health challenges facing children and families in their community settings. These
partnerships would not be complete without the health care community. Today, this collective network of
research, community, and clinical partners can be proud of the training and development programs that
are preparing future scientists and health care professionals, including residents, fellows, and academic
physicians in becoming tomorrow's experts and leaders in CEH.
SESSION I: EVOLUTION OF BIOMARKERS FOR PESTICIDES: EXAMPLES FROM THE
AGRICULTURAL SETTING
Co-Chairs: Catherine Karr and Elaine Faustman, University of Washington
Dr. Karr stated that it was a pleasure to open the first workshop session. The topic of the session is the
evolution of biomarkers for pesticides with examples from agricultural settings. The session speakers are
accomplished leaders from the public health, research, and clinical sectors who will discuss their experi-
ences with biomarkers with the focus on a specific group of pesticides, the OP insecticides. Despite recent
decreases in home and garden use, these insecticides continue to be used heavily in agriculture and are of
great interest in the Pacific Northwest because of orchard crop production that relies intensively on OP
use. OPs also are of interest because of their legacy of acute toxicity in humans; they are the pesticides
most often implicated in symptomatic illness. Another reason to consider OP exposures is the
accumulating evidence of neurodevelopmental toxicity related to relatively low chronic exposures in
children. This provides a framework for considering the application and use of biomarkers. Biomarkers
provide a context for understanding the pathway from release of an organopesticide in a child's
environment to the potential for development of clinically significant disease or prognosis. This session
will explore biomarkers of exposure in terms of internal dose measures using urinary metabolite
monitoring, biomarkers of biologically effective dose or early biological effect, and biomarkers of
susceptibility based on genetic polymorphisms in the population.
PEHSUs receive a number of questions from parents, pediatricians, public health officers, federal agency
leaders, and policy-makers from "Should I have my child tested?" to "Should we have a national
monitoring program for agricultural workers?" Today researchers are at the stage of validating
biomarkers and must concentrate their efforts on finding ways for various sectors to utilize these data.
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Efforts to use biomarkers in population-based monitoring in the States of Washington and California for
occupational surveillance may inform the following questions: Should we have a national medical
monitoring program for agriculturally exposed workers? What would such a program constitute? Lastly,
from a risk assessment perspective, policy-makers may ask researchers: Can we use biomonitoring to
evaluate whether regulation of diazanon and chlorpyrifos (CPF) has reduced exposure in at-risk
populations such as children? Policy-makers may follow the unfolding story of the paraoxonase gene
(PON1) as an effect modifier and ask: Should regulatory decision-making incorporate evaluation and
protection of the most genetically vulnerable subset of the population? These are questions to consider
during the presentations. The presenters will provide insight into progress toward validation of
biomarkers and their utility as well as various limitations and knowledge gaps that need to be overcome,
so that researchers can move forward to increase the clinical public health and risk assessment relevancy
of biomarkers.
Biomarkers of Pesticide Exposure: Lessons for Children in Agricultural Communities
Elaine Faustman, University of Washington
Dr. Faustman stated that her presentation would focus on some of the biomarkers of pesticide exposure
and some of the lessons for children in agricultural communities, including exposure to internal dose,
biologically effective does, early biological effect, altered structure and function, clinical disease, and the
relationship with biomarkers of exposure and biomarkers of effect. In Washington State, OPs are used on
apple and potato crops. OPs have various structures that differ by ethyl and methyl moieties, and up to 40
different OPs are in common use. The differences in patterns of the methyl and ethyl group metabolites
can allow for the tracking of sources and attributable uses of these pesticides. Linking this information
within the exposure response biomarker paradigm is important. Agricultural pesticides and contributions
of occupational factors to home, adult, and child contamination will be discussed.
The complex series of metabolites that are formed following OP exposure presents a challenge to
examining and interpreting what a biomarker of exposure might mean from the environment versus an
internal dose of biomarker (e.g., urinary metabolites). Genetic polymorphism in the enzymes involved in
the metabolism of these compounds present significant challenges, but modeling approaches that measure
specific and nonspecific metabolites from OPs allow researchers to compare exposure markers. National
Health and Nutrition Examination Survey (NFIANES) data show U.S. population averages and show that
children's exposures are higher than average adult exposures, and this becomes important if the exposures
remain elevated over multiple years. In terms of assessing children's exposure based on the take-home
pathway, this is the hypothesis that was put forth: Adult workplace exposure increases pesticides in dust
in vehicles and homes and, therefore, to children through direct physical contact with the adults and
indirectly through contaminated homes and cars. For example, a study of homes and vehicles of
farmworkers in the Pacific Northwest found that the workers had higher levels of pesticides in the dust of
their vehicles and homes and OP markers one to two orders of magnitude higher than U.S. averages.
Their children's levels also were skewed to higher values compared with NHANES data. Modeling across
specific metabolites allows researchers to detect high-risk exposure subgroups. Another study examined
various crops and the distributions of specific metabolites in nonfarmworkers and farmworkers adults and
children. Results showed a higher association of OP metabolites among those working with pome fruit,
and this was identified as a potential place for intervention. All of the correlations were positive,
illustrating a strong workplace take-home pathway. Using these models, sources of where the metabolite
was attributable to child exposure were identified. These data have informed decisions about intervention
procedures and allows targeting of populations that have been neglected in terms of public health
intervention.
Two longitudinal studies measuring OP metabolites revealed another issue involved in biomarker
analyses: variability. The variability was less between children than the variability within an individual
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child; metabolites will vary considerably following repeated sampling of children. Within-person
distributions are wider than distributions among a whole population. This has important ramifications in
understanding the potential environmental effects of certain agents. Because there are a variety of factors
(e.g., half-life, dynamics of exposure, and continued exposure), sampling approaches must be considered
that increase understanding of how individuals versus populations are being exposed.
Biomarkers of exposure cannot be used for all types of studies, but they are very useful for understanding
the patterns of exposures and source attribution. Other studies may be necessary to identify highly
exposed groups and plan interventions. EPA studies will allow researchers to link multiple sampling of
exposure and internal dose with potential early markers of response, such as enzyme changes and gene
expression markers. Physiologically based toxicokinetic models are being built for OPs, with
polymorphic information being added at multiple stages for the myriad of enzymes that are involved in
OP metabolism. This is important so that genotypes can be used to help identify at-risk populations and to
determine what these differences may mean for exposure and responses. Once these tools are further
developed, they can be used for research and clinical applications. Dr. Faustman's group will be testing
the hypotheses of how much knowledge about the genotype-phenotype makes a difference in
understanding differences in between-person variability and how much knowledge about gene expression
contributes to understanding responses within the same person over time. Future work includes
identifying the genotype and phenotype for key genes that metabolize OPs to improve prediction of
exposure response and at-risk individuals in agricultural communities. Learning more about
polymorphisms of oxidant responsive pathways will allow researchers to better evaluate the potential for
genomic biomarkers of early response to be linked with OP metabolites of exposure, better predict
relationship of biomarkers of effect (e.g., acetylcholine) to respond in a dose-response manner to OP
exposures in adults and children, and better predict whether "omic" biomarkers of disease are correlated
with OP exposure.
Discussion
A participant requested clarification on the comment regarding how exposure measurement techniques
may need to be modified for assessment of chemicals with short chemical half-lives. Dr. Faustman replied
that the NCS holds a lot of promise to look at longitudinal exposures, but there are unique questions for
some agents, for which the exposure and compounds are dynamic enough that additional assessments
could be used in the NCS to answer some of these more specific questions. Her presentation illustrated
the kind of information that can be gained from longitudinal studies versus specific studies and how this
information can be integrated to build a cohesive picture.
A participant asked if the study examined children under age 6. Dr. Faustman replied that the study
included younger children but did not examine crawling behavior.
A participant asked Dr. Faustman to discuss intervention and evaluation studies regarding the take-home
pathway conducted at the University of Washington Center. Dr. Faustman indicated that a paired study
was conducted where interventions were performed at the community- and household-level. The data are
being analyzed, but early results show positive associations with intervention actions taken in the homes.
OP Pesticide Exposures and Neurodevelopment in Children From Farmworker Families
Kim Harley, University of California at Berkeley
The Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study is a
longitudinal birth cohort study of Mexican farmworker children and their mothers in the agricultural
Salinas Valley region of California. The goals of this study were to: (1) estimate source and pathways of
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OP pesticide exposure and levels of in utero and postnatal pesticide exposures in children living in
agricultural communities; and (2) determine the relationship of this exposure with neurodevelopment,
growth, and respiratory disease. The Berkeley team measured biomarkers of OP exposure using
dialkylphosphate (DAP) metabolites measured in maternal and child urine. Increasing age, proximity to
agricultural fields, and increased consumption of fresh fruits and vegetables were associated with higher
DAP levels in young children in this cohort. Prenatal and child DAP levels were compared with early
childhood neurodevelopmental and neurobehavioral outcomes using the Brazelton Neonatal Behavioral
Assessment Scale, Bayley Scales of Infant Development, the Wechsler Preschool and Primary Scale of
Intelligence (WPPSI-III), and the Child Behavior Checklist (CBCL). Reflexes in neonates were more
likely to be abnormal in association with high maternal DAPs, but no associations were established
between prenatal DAPs and six of the other seven Brazelton clusters. In addition, as the mothers' prenatal
levels increased, Bayley Mental Development Index scores decreased in children at 24 months of age.
Higher prenatal DAPs were also associated with increased likelihood of Pervasive Developmental
Disorder, as assessed by the CBCL at 24 and 42 months of age. Findings were driven primarily by the
dimethylphosphate, as opposed to diethylphosphate metabolites. These results were compared with
similar studies at Mt. Sinai Hospital and Columbia University in New York City (NYC). Although these
studies looked at different populations, the results mirrored results found in California. The NYC cohorts
were made up of Mexican, Puerto Rican, and Dominican Hispanics; African Americans; and non-
Hispanic Whites in an urban environment. The majority of the Berkeley cohort was comprised of
Mexican Hispanics from an agricultural environment. Despite these differences, some patterns have
emerged across these three cohort studies. Prenatal OP exposures in two cohorts were associated with
increased odds of abnormal reflexes in neonates, and in all three cohorts with poorer mental development
in 2- and 3-year-olds and poorer verbal IQ in 3.5-5-year-olds. Increased odds of pervasive developmental
disorder was found in the two cohorts that examined this outcome.
Discussion
A participant asked if fruit and vegetable consumption could explain better performance in children.
Dr. Harley responded that fruit and vegetable consumption was factored into the model and did not
account for any differences.
A participant asked about potential confounders in the study. Dr. Harley answered that the study adjusted
for factors that could have a bearing on development and intellect (e.g., parental IQ, socioeconomics,
etc.).
A participant commented about the findings of a rat study that showed higher performance levels
associated with CPF exposure and suggested that the researchers examine the higher performing children
in the study to determine if they had higher prenatal exposures.
Cholinesterase Monitoring in Washington State
John Furman, Washington State Department of Labor and Industries
In 2003, the Washington State Department of Labor and Industries began an occupational medical
surveillance program of agricultural pesticide handlers that measured cholinesterase (ChE) levels
throughout the pesticide application season to detect overexposure to pesticides and prevent illness,
increase hazard awareness, identify unsafe environments, and fix problems. Symptoms of ChE illness
range from mild to severe and include dizziness, blurred vision, nausea, headache, stomach cramps,
diarrhea, hypotension, and seizures; often, many of these symptoms are misdiagnosed.
Acetylcholinesterase is an enzyme that removes the chemical neurotransmitter acetylcholine from the
neuronal synapse. Humans, insects, and other species have this basic acetylcholine system.
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Cholinesterase-inhibiting pesticides have been developed to kill insects, but overexposure in humans
results in sustained levels of acetylcholine and overstimulation of neuronal pathways and eventual
exhaustion of neuronal pathways. Pesticide handlers of Toxicity Class I and II pesticides are monitored
for ChE levels in red blood cells (RBCs) and serum. Exposure-free baselines are established annually
during periods when handlers have not handled pesticides for at least 30 days. Analyses are conducted
within the same laboratory to control for interlaboratory variations. Employees who handle these
pesticides for more than 30 hours in any 30-day span are tested every 30 days. Employees may decline
participation but must undergo an informed consent process with a medical provider if they opt out. ChE
depression of 20 percent or more from baseline requires the employer to perform a work practice
evaluation and intervene to reduce any chances of further exposure. Depression of 30 percent or more in
RBC CheE or 40 percent or more in serum ChE requires the employee to be removed from handling until
their levels return to within 20 percent of baseline. In addition to monitoring and enforcement, the
program also provides follow-up services for those with significant ChE depression and consultation
services to employers to help them reduce further exposures, reduce possible risk of long-term adverse
health effects, and decrease take-home exposures. These follow-up efforts are offered to employees and
employers even if they no longer participate in the program. The program has led to increased knowledge
on the use of these pesticides, increased hazard awareness, changes in pest management practices, greater
access to medical services, and more informed diagnoses and treatment of pesticide-related illness.
Additionally, the findings of this program are being integrated into a state-wide pesticide handler training
program.
Discussion
A participant requested clarification on the percentage of employees declining participation with the
program. Dr. Furman replied that the program is averaging a 12 percent declination rate, and there has
been a sustained participation during the past 3 years.
A participant asked about the change in minimum hours of handling for workers to be tested. Dr. Furman
responded that the initial recommendation by the researchers was 30 hours, but political intervention
arrived at the 50-hour minimum. No significant correlations were found between handling hours and ChE
depression after 3 years of testing; however, a legal suit forced the issue, and the hours have been changed
to the initial recommended minimum of 30.
A participant asked if OP pesticides are being replaced by other pesticides. Dr. Furman answered that part
of the program follow-up procedures capture this information, and a significant number of employers who
were previously engaged in the program have switched to safer products.
A participant asked about published findings that demonstrate that these types of interventions lead to
health outcomes and behavior change. Dr. Furman replied that research reports for each of the 3 years are
posted at http://www.lni.wa.gov/Safety/Topics/AtoZ/Cholinesterase/default.asp.
Biomarkers of Pesticide Exposure: Lessons for Children in Agricultural Communities
Catherine Karr, University of Washington
Dr. Karr discussed the utility of ChE testing in clinical practice as a diagnostic tool for identifying
pesticide poisoning in children. Although significant exposure occurs in agricultural workplaces,
playgrounds, and orchards in agricultural Pacific Northwest, poisoning is not always considered by
pediatricians. When it is suspected, it is difficult to interpret cholinesterase tests because there often is no
baseline with which to compare it. Additionally, while cholinesterase tests are useful for diagnosing or
confirming OP poisoning, there is no test for detecting chronic exposure, which may have health
implications. In addition, while the symptoms in classic adult occupational poisoning have been
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identified, in children they are not so clear, making diagnoses in children more difficult. Overexposed
children are much more likely to manifest central nervous system (CNS) symptoms, and very young
children cannot verbalize these symptoms and often present with subtle signs. Children are more likely to
develop seizures as a result of OP poisoning. The classic hypersecretion (e.g., tearing, diarrhea, urinary
incontinence, sweating) seen in adults often is not seen in children, and the poisoning is misdiagnosed as
a more common infectious illness, such as flu or gastroenteritis.
Although there is great variability in the normal population, ChE testing still can play a role in the context
of post-exposure followup testing, which can discern if there were significant changes in an individual.
ChE testing is useful for acute OP poisoning via the cholinergic pathway, but there is evidence that
neurodevelopmental toxicity can occur by alternate mechanisms. In vivo embryonic and neonatal rat
models and neuronal rat cell line studies show effects seen throughout brain regions, including those with
very little cholinergic innervation. Cell loss and apoptosis occurs immediately after exposure, neural
deficits appear later in adolescent and adult animals, brain cell numbers are reduced, and neurite
projections and synaptic communications are disrupted. This translates into a disruption of signaling
pathways that are very important for normal neurological development in children and immature animals,
and it is thought that these may underlie some of these observations in the epidemiological studies, such
as effects on performance, attention, and behavior in humans.
A targeted survey in Washington State was conducted of healthcare providers and promotoras (lay health
providers) who serve farm families and farmworkers in agricultural regions. Results showed that 49
percent of respondents had received any training on pesticides and health, and 22 percent had received
child-specific information on pesticides and health. Based on these findings, the Washington PEHSU, in
collaboration with the Pacific Northwest Agricultural Safety and Health Center, developed a Web-based
CME product, "OP Pesticides and Child Health: A Primer for Healthcare Providers," which includes
translation of findings from the NIEHS/EPA CEHCs regarding chronic toxicity. Additionally, in-person
training has been conducted for promotoras who did not show an interest in the Web product.
Dr. Karr ended her presentation by raising some questions to motivate moving beyond ChE testing and
focusing further on noncholinergic endpoints. She indicated the need for more rapid tests that can be used
in clinical practice to confirm acute exposure to OPs and help provide indication for preventive guidance
to parents. Finally, she urged participants to begin thinking about OP exposures in children with
neurodevelopmental disabilities (e.g., ADHD or autism). In addition to potential etiologic relationships,
these subgroups may be particularly vulnerable to the toxicity of OP exposure.
Integrated Pest Management in New York City Public Housing
Frederica Perera, Columbia University
Dr. Perera outlined some of the studies being conducted at the Columbia Center for Children's
Environmental Health. Based on high levels of CPF exposure, as measured by plasma concentrations in
mothers and newborns in the Columbia cohort, the researchers instituted: (1) an educational intervention
with newsletters to members of the cohort and community; (2) an integrated pest management (IPM)
project; and (3) an effort to develop an early life reference dose (RfD) of OPs. Levels of use of CPF are
down, following the EPA phaseout for residential use, and the Columbia study recorded a significant drop
in plasma levels of chlorpyrifos in umbilical cord blood. High prenatal exposure, as measured by elevated
umbilical cord levels, was associated with a decrease in developmental scores at 3 years using the Bayley
Scales at age 3, and at 5 years using the WPPSI. The adverse effect was observed with the highest
concentrations of CPF occurring before the EPA ban.
The IPM intervention was formed through a partnership with the NYC Department of Health and Mental
Hygiene and the NYC Housing Authority. It involved professional cleaning to remove food sources and
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cockroach frass (fecal matter) in kitchens and bathrooms of 194 intervention and 129 control apartments.
Following intervention, cockroach populations were decreased, allergens were significantly decreased,
and nearly a 50 percent decrease was seen in the use of bombs and sprays by the IPM group. Effects on
asthma symptoms are being evaluated. Based on these results, the housing authority is expanding the IPM
to other building sites in NYC.
Use of Biomarkers and Physiologically Based Pharmacokinetic (PBPK) Modeling
in Risk Analysis for Developmental Effects of Chlorpyrifos
Robin Whyatt, Columbia University
The newly received EPA Science To Achieve Results grant is designed to use the exposure response
relationship seen in the Columbia study and, using PBPK modeling, derive an RfD dose for CPF based on
the developmental effects of the maternal dose during pregnancy. The study approach is enhancing an
already-developed CPF PBPK model to estimate dosimetry during pregnancy. It will incorporate human
interindividual variability in key metabolic parameters, based in part on newer metabolism measurements
in human livers and exposure time pattern data to convert observed CPF levels in cord and maternal blood
to both intake doses and internal concentrations of active metabolite for benchmark modeling. The
specific measurements to be used from the Columbia study include cord blood levels of CPF at delivery,
maternal blood levels 1-2 days following delivery, indoor and personal air levels of CPF, and urinary
levels of a CPF metabolite (TCPY). These data will be used with NHANES data to estimate what
percentage of the population in the United States has detectable levels of CPF in their urine. More
information on this study can be found at http://www.mailman.hs.columbia.edu/ccceh/about.html.
Discussion
A representative from the New England Asthma Regional Council offered information about research on
the effectiveness of IPM, particularly for homes in low-income populations, that was translated into
policies and procedures. In conjunction with HUD, the New England Council will be releasing a DVD for
tenants and housing managers on how to use IPM. In addition, over the next few months, the Council will
be releasing a toolkit for policy-makers on how to promote IPM from a policy level on federal, state, and
local levels and a toolkit for housing managers on how to work with their tenants to put IPM into place
using the Boston Housing Authority's successful model. More information can be found at the New
England Asthma Regional Council Web Site (http://www.asthmaregionalcouncil.org).
SESSION II: PHTHALATES EXPOSURE IN CHILDHOOD: Is THERE EVIDENCE OF HARM?
Chair: Maida P. Galvez, Mount Sinai School of Medicine
The goals of this presentation were to describe phthalate exposure levels in pregnant women, toddlers,
and school age children; identify important sources of exposure in these populations; and understand the
known and potential health outcomes. Based on exposure studies in animals, there is evidence for adverse
birth outcomes, from fetal demise to modulation of gestational age to adverse impacts on the male
reproductive system, including decreased anogenital distance in male infants and decreased testicular
function and fertility. Phthalates are found in a wide range of products, and there is potential for
inhalation, ingestion, and dermal absorption, the major pathways of exposure. The premature baby
population, which is exposed through medical IV tubing in intensive care units (ICUs), is considered
highly sensitive to exposures. The potential of phthalates to act as endocrine disrupters is a concern, based
on animal studies and a small but growing body of evidence in human studies.
Legislation banning phthalate use in children's toys was first implemented in the European Union, and
subsequent media reports raised parental anxiety about a number of items in their homes that may
potentially expose their children. Primary pediatric physicians are in a difficult position, faced with
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clinical questions that are difficult to answer. Pediatricians receive limited training in CEH in medical
school, have limited knowledge of emerging exposures of concern such as phthalates, and are exposed to
conflicting messages in the media. Dr. Galvez concluded her presentation by introducing the speakers for
this session.
Phthalate Exposures During Pregnancy
Robin Whyatt, Columbia University
The Columbia Center for Children's Environmental Health is conducting research on phthalate exposure
during pregnancy from inner city communities in NYC because it is a universal issue in the United States.
A number of phthalates are endocrine disrupters, including those acting as anti-androgens. Experimental
and epidemiological evidence indicates that a number of phthalates are reproductive toxicants and are
associated with malformation in the developing male reproductive tract and other reproductive outcomes.
Recent epidemiologic data indicate that prenatal exposure may modulate the timing of labor.
The specific aims of the research are to: (1) characterize phthalate exposures during pregnancy among
NYC African American and Dominican women (n = 350); (2) examine effects of prenatal phthalate
exposures on modulation of gene expression in placental tissue; and (3) examine the effects of prenatal
phthalate exposure on gestational age and fetal growth. This cohort is comprised of 300 mother-newborn
pairs from a larger 725-person cohort and has the same inclusion/exclusion residential criteria as the full
cohort. Phthalates were measured in personal air samples during pregnancy, and biological samples and
gene expression were examined. The conclusions of this study are that phthalate exposures are
widespread among NYC African Americans and Dominicans during pregnancy; phthalates are detected in
85-100 percent of indoor air, personal air and maternal urine samples; indoor air levels appear stable over
time and are significantly correlated with personal air levels in most cases; there is a significant
correlation between air and urine levels in two phthalates; and di(2-ethylhexyl)phthalate (DEHP) expo-
sures may be modulating gestational age.
Discussion
A participant asked about data on the time of urine collection in relation to when the mothers may have
been using cosmetics. Dr. Whyatt responded that these data have not been analyzed for diurnal variability.
A participant asked about air fresheners, because many of them contain phthalates, including those
labeled as "all natural." Dr. Whyatt indicated that they collected extensive questionnaire data related to
product use, but the data have not been analyzed in relation to outcome measures. There is such
variability between products and within brands of products that the questionnaires may not be capturing
the intended information.
A participant asked if the study will be expanded beyond minority populations. Dr. Whyatt explained that
there are no plans to extend the study beyond the Center's cohort, but phthalate studies are being planned
for the Krakow cohort.
Infant Phthalate Exposures and Potential Developmental Impacts
Sheela Sathyanarayana, University of Washington
The University of Washington and Northwest PEHSU, in concert with the University of Rochester,
examined data from the Study for Future Families, a mother-baby cohort study in Missouri, California,
and Minnesota, to determine whether infant personal care product use was associated with urine pthalate
concentrations and whether maternal phthalate exposure was associated with developmental outcomes in
infants. The demographic characteristics of the cohort study included 163 infants ages 2-24 months, with
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an even distribution between genders; a racial profile of 80 percent white and 11 percent Hispanic and
Latino; high socioeconomic status; 50 percent of participants from Minnesota and 25 percent each from
Missouri and California; and 91 percent of families reporting health insurance. Infant urine samples were
tested for detectable concentrations of nine known phthalate metabolites, and all infants samples
contained at least one detectable phthalate metabolite. More than 80 percent had detectable concentrations
for seven of the metabolites, and over 50 percent showed detectable concentrations for all nine. These
concentrations are similar to or lower than children 6-11 years of age in NHANES data. This may be
because younger children are not as involved in their environments unless they are walking or crawling;
therefore, most of their exposures come from their parents and diet. Metabolites were measured to test for
an association with reported use of a variety of baby products, including baby powder, baby lotion, baby
shampoo, diaper cream, and baby wipes. Infants whose mothers reported using baby lotion, shampoo, and
powder showed increases in urine phthalate metabolites compared to infants who were not exposed.
Results of this study suggest that phthalate exposure in infants is widespread, distribution is varied in
infants, and dermally applied baby care products may significantly contribute to infant phthalate body
burden. Reported exposure to baby lotion, baby powder, and baby shampoo was significantly associated
with increased urinary concentrations of monoethyl (MEP), monobutyl (MMP), and monoisobutyl, and
the associations were stronger in younger infants.
To determine whether maternal phthalate exposure was associated with developmental outcomes in
infants, the researchers examined anogenital distance as a marker in infants because of animal model
evidence that abnormal anogenital distance is associated with phthalate exposure and genital tract
abnormalities. Exposure in rodents is related to shorter anogenital distance, impaired testicular descent,
hypospadia, low sperm count, and sometimes testicular tumors. Because short anogenital distance is the
most important marker, the researchers first created a model estimating the standard for distance
associated with age and weight. The phthalates associated with the shorter distance included MBP, MEP,
and DEHP phthalate metabolites. Increasing phthalate metabolite concentrations were associated with
decreasing anogenital distance in a dose-response manner. The clinical implications of these findings
associated exposure with a shorter anogenital distance and suggest that phthalates may act through an
endocrine disrupting mechanism to affect hormonal development of genital structures. Researchers also
found an association between increased phthalate metabolite concentrations, decreased testicular descent,
and smaller penile volume, but these were not significant. Further research is needed to determine if
distance is a marker of abnormal male reproductive development in humans.
Discussion
A participant asked why an earlier study did not find a metabolite effect. Dr. Sathyanarayana indicated
that the sample size was not large enough for that study, and that they had used the anogenital index,
which was not an appropriate statistical model for predicting the expected distance. Based on feedback to
the earlier study regarding these issues, the research team for this study constructed a new age- and
weight-based model for conducting analyses, but the results of this study have not yet been published.
A participant requested clarification on the hormone involved in these studies and asked if phthalates
could be tested for with amniocentesis. Dr. Sathyanarayana explained that the theory is that androgen
decreases overall in utero as a result of exposure, but it is difficult to determine whether it is testosterone
or some other hormone. One problem with using amniocentesis for phthalate detection is that the
procedure is not a standard test, and it is usually carried out on high-risk pregnancies, decreasing its
feasibility as an accurate marker for the general population.
A participant asked about the specific components of the baby products that are associated with phthalate
exposures. Dr. Sathyanarayana replied that there is no method to determine the components because there
are no labeling requirements for chemicals, which is why studies that identify phthalate-associated
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products are important. California is beginning to mandate disclosure of phthalates and other reproductive
and carcinogenic compounds for products sold in that state. In addition, phthalates are plasticizers that
help bind other compounds together, so it is possible that the manufacturing process may be responsible,
not necessarily the product components.
A participant asked whether synthetic hormone use during pregnancy was controlled for and whether any
of the male infants had hypospadias or cryptorchidism. Dr. Sathyanarayana responded that the mothers
were asked about hormone use during pregnancy, and all reported no use. None of the boys had frank
phenotypic abnormalities.
A participant asked whether the U.S. Food and Drug Administration (FDA) had examined this study and
set a maximum level in all these products. Dr. Sathyanarayana answered that the FDA has evaluated
phthalates previously and has not set any concentration levels, but as the results of this study have not
been published, the FDA has not examined the data. The FDA did register a warning to health care
providers that concentrations might be high in neonatal ICUs because of IV tubing, but the agency has not
set any mandatory requirements for testing or RfDs. EPA will be undertaking a larger review soon.
Another participant clarified that the FDA receives advice from a separate industry-run organization but
does not have authority over cosmetic products. The European Union has banned phthalates in many of
these products, which may be pushing U.S. industries to produce phthalate-free products because they
market to the European Union. One cautionary note regarding phthalate-free products on the market is
that consumer companies still find detectable levels in these products; there must be a higher level of
enforcement at some point.
Inner City Toxicants, Child Growth and Development
Mary Wolff, Mount Sinai School of Medicine
Dr. Wolff mentioned a monograph published by Environmental Health Perspectives in the 1970s that
proved phthalates are not toxic. The issue now is that the levels of phthalates are very high and that some
of the newer generations of bioassays have revealed hormonal effects. She summarized preliminary data
from the Mt. Sinai birth cohort, a multiracial cohort that included 100 boys and 300 girls from 6-8 years
of age. The researchers conducted exposure assessments in mothers during their third trimesters and
outcome measurements of the children. In a cohort of school-age children, levels and variability have
been assessed to determine feasibility of a single urinary biomarker for these chemicals. Preliminary
results showed exposures similar to the Columbia study for MEP. The mothers had higher levels of some
phthalate metabolites than the Columbia and NHANES cohorts, but were consistent with NHANES for
minorities. Results of temporality studies suggest that some of these biomarkers can be used as predictors
of these metabolites for up to 1 year, and of the three families of chemicals studied, phthalates were the
most reproducible. The Mt. Sinai team also summed groups of phthalates based on molecular weight and
found significant levels of low molecular-weight phthalates among the minority populations and higher
molecular weights among whites. Product use questionnaires revealed some borderline associations of the
DEHP metabolites with nail polish and hair products, but they were not significant in preliminary data
from a small number of subjects.
Because there currently is much interest in body mass index (BMI) and phthalates because of cross-
sectional data published by NHANES, the researchers examined gestational age. In relation to phthalate
metabolites, the researchers found very weak associations between phthalate exposure and longer
gestation. The researchers currently are evaluating these biomarkers with respect to neurodevelopment.
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Discussion
Dr. Maida Galvez summarized the presentations before opening the floor to discussion. Phthalate
exposures are widespread. In this session, evidence was presented from three different cohorts, ranging
from exposures in pregnancy, a particularly vulnerable time period, through early childhood and beyond.
The two cohorts of pregnant women from NYC showed similar levels of exposure, despite the fact that
the populations were very different in racial and ethnic demographics. This is a contrast to exposures in
infancy and early childhood in a predominantly white cohort, with relatively low exposures when
compared to the inner city populations. The sources of exposure were varied, from voluntary use of
products to contamination of indoor air from dust generated from phthalate products. Through measure-
ment of the available biomarkers, there is now limited evidence from human studies demonstrating
possible modulation of gestational age and potential impact on anogenital distance. These cohorts will
continue, and effects on body size, particularly BMI and waist-hip ratio; potential associations with
asthma; and other developmental outcomes will be examined. What to tell the parents asking for advice is
a challenging situation, but it is usually best to give them an action item in the face of clinical uncertainty.
Mt. Sinai's Community Outreach Translational Core developed a pocket guide to plastics for easy
reference. In the absence of legislation mandating correct labeling of products, these wallet-size cards can
help families identify phthalate-containing products. In general, the plastics to avoid are labeled 3, 6, and
7 for recycling purposes. The CEH community needs to work together to determine the best health
messages to relay to families and what policy issues to advocate.
A participant asked about the Mt. Sinai study participants' access to results. Dr. Wolff explained that
participants were provided with summary data when available on request. Families also would be told
how their levels compared to the entire study population on request, but no individual data would be
shared with the participants. The researchers were prepared to respond to questions through a potential
collaboration with the PEHSUs, but no requests have been received. Study participants did express
concern that environmental factors may be related to long-term health outcomes such as obesity and
puberty. The same question was posed to Dr. Sathyanarayana, who replied that study participants
received a one-page handout of the previously published study because the current study results are not
complete. Dr. Wolffs team will not be submitting individual data, but its cohort was educated about
group findings versus individual findings at enrollment. The participants were told that if harm is found
on a group basis, the entire cohort would be notified about those findings and receive information on what
they could do on an individual basis to reduce the exposure.
A participant asked about the issue of potential "sleeper biomarkers" that have been identified in animal
models but have not been tested in humans. One of the session speakers answered that some studies are
underway, and an issue remains regarding validation involved in anthropological types of markers, such
as anogenital distance. Some clinicians successfully use the finger ration with certain conditions (autism,
etc.) and the results are very interesting but difficult to measure scientifically. Another participant added
that a new mulitcenter cohort study is underway that uses anogenital distance to examine dysmorphology.
A participant asked for clarification on what the focus was of the pocket guide. Dr. Wolff explained that
the pocket guide identifies plastics that are associated with phthalates and other chemical exposures from
food packaging. Because dietary sources are considered to be the major pathway of phthalate exposure,
the card also includes some information about leaching.
A participant questioned the usefulness of cautioning the public about phthalate-free products, because
although organic food contains detectable levels of pesticides, it is still considered better because the
levels are relatively lower. Dr. Galvez indicated that, from the limited consumer product testing,
phthalate-free products do contain relatively lower levels of phthalates, but the study participants received
cautioning as a process of full disclosure so they could make informed decisions.
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A participant asked, given the relatively small effect size in much of the presented data regarding which
plastic containers or which kind of fragrant-free products to use, where clinicians should put this issue on
the list of priorities when discussing hazards with parents. A session speaker explained that, although
there is no definitive answer regarding humans, it is not a good idea to put phthalates on the bottom of the
priority list in a clinic setting. Animal toxicity data exist, and more studies are planned. Full disclosure
about what is known and what is not known is better than no disclosure.
A participant commented that the benefit of the CEHCs is that they bring clinicians and the community
together in an academic setting where there is integration of mechanistic and animal scientists. Anogenital
distance studies were prompted by animal studies. Increased collaboration between animal scientists and
human health and environmental researchers will increase opportunities for the CEH community to learn
about biomarkers. Perhaps more of the animal models will be adapted to human studies for more
definitive purposes.
A participant asked if there is a safer substitute for phthalates. A session speaker explained that there are
other plasticizers and other technologies that do not use a plasticizer, but there are enormous data gaps on
the substitutes. Nonplasticizers do not leach as much as plasticizers, so that may be a significant
advantage. Dr. Wolffs team is preparing to submit a paper examining substitutions in the neonatal ICU
because that is where exposures are higher. The paper examines every substitute to date and what is
known about them.
SESSION III: THE EVOLVING SCIENCE AND PRACTICE OF ENVIRONMENTAL MANAGEMENT
FOR ASTHMA PREVENTION AND CARE
Co-Chairs: Kimberly Gray, NIEHS, andLeyla E. McCurdy, National Environmental
Education Foundation
Improving Asthma Outcomes: 2007 NAEPP Guidelines Focus Attention on Education and
Environmental Interventions
David Rowson, U.S. EPA
Mr. Rowson provided an overview of the 2007 National Asthma Education and Prevention Program
(NAEPP) Guidelines for the diagnosis and management of asthma. The new guidelines focus on
monitoring asthma control as the goal for asthma therapy and distinguishing between asthma severity and
monitoring asthma control. Treatment should be initiated based on severity assessment and then adjusted
based on control. There is a new focus on impairment and risk. Impairment includes the frequency and
intensity of symptoms, low lung function, and activity limitations. Future risk includes the risks of
exacerbation, progressive loss of lung function, or adverse side effects from medications. Clinicians need
to increase the consistency of asthma monitoring, assessment, and care. There are new modifications to
the step-wise approach to long-term management of asthma. Treatment is partitioned into three different
age groups, and there are six specific steps of care that span from intermittent to severe. The new
guidelines incorporate updated approaches to patient education and control of environmental factors and
co-morbid conditions that affect asthma. Finally, there are modifications to treatment strategies for
managing and classifying asthma exacerbations. The guidelines are built around a framework of four
essential components that include: (1) assessment and monitoring of asthma severity and control;
(2) education for a partnership in asthma care; (3) control of environmental factors and co-morbid
conditions; and (4) medications.
The new guidelines have increased attention on self-management and education of family and individuals
regarding the environment, noting many potential sites for asthma education and care: homes, schools,
and community settings. The guidelines recommend patients receive education in an integrated,
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multifaceted method in multiple settings. Written action plans are highlighted as a central component of
asthma care, with a focus on multicultural ethnic factors and health literacy to enhance adherence to
physician advice and medication regimens. Provider education also is highlighted as an essential
component. Automated assistance helps clinicians to adhere to the guidelines, so these systems are being
put into place to support them. The most important actions patients should take include avoiding
environmental triggers that exacerbate symptoms and cause asthma attacks. The guidelines list potential
triggers and a series of steps to follow for controlling individual environments. The guidelines
recommend testing individuals for sensitivities so that intervention steps can be tailored to individual
needs. The guidelines also stress the importance of an active lifestyle. With proper control, exercise
should be possible; if an individual cannot exercise because of symptoms, that should be considered a
benchmark for a change in treatment.
Although asthma rates appear to be steadying nationally, they remain at an all-time high, and there are
significant disparities in morbidity and mortality. Healthy People 2010 goals contain a range of important
indicators; some of those goals are close to being reached, whereas others are farther off. The new
guidelines highlight critical areas to help reach those goals. For instance, the guidelines suggest more
written asthma action plans, increasing adherence with treatment, and controlling for environmental
triggers—all goals ofHP2010.
To support the delivery of evidence-based care at the community level, EPA is supporting the
Communities in Action for Asthma Friendly Environments Network (CAAFE). Grounded in the results
of the Asthma Health Outcomes Project and conducted by the University of Michigan, a centerpiece of
CAAFE is the Change Package—a compendium of practical, day-to-day best practices program strategies
that deliver positive health outcomes. CAAFE is supported by an interactive Web site developed to
facilitate real-time learning and sharing of best practices, as well as an annual National Asthma Forum.
More information on the CAAFE and the National Asthma Forum can be found at
http: //www. asthmacommunitynetwork.org.
Prenatal and Early Postnatal Exposures and Asthma Risk—How?
Rachel Miller, Columbia University
Dr. Miller provided a review of mechanistic data that begin to address the question of how prenatal and
postnatal exposures may affect asthma risk. Asthma is a complex disease mediated by genetic
predisposition, environmental exposures, and host factors (e.g., obesity, psychosocial issues, infections).
Prenatal and early postnatal exposure (e.g., traffic, diesel, roaches, dust mite allergens, pollens) can
modify asthma risk, and there is evidence that exposure during pregnancy is very important in modifying
or protecting for asthma. A review of epidemiologic data shows that prenatal exposure can affect asthma
risk, and the strongest evidence is related to prenatal exposure to environmental tobacco smoke (ETS).
Prenatal ETS exposure is associated with impaired respiratory function, transient wheeze, asthma, and
respiratory infections in infants and young children. Additional exposures during pregnancy that appear to
be associated with an increased risk of asthma include low maternal intake of vitamin E and zinc during
pregnancy, antibiotic use, and several types of maternal infection. Furthermore, respiratory infection
during pregnancy has been shown to be an independent factor that may increase later asthma risk. Recent
data also suggest that ambient air pollution and polycyclic aromatic hydrocarbons may increase risk later
on in life for children. Early postnatal exposure to traffic and combustion-related pollutants has been
associated with both dust mite sensitization and impaired pulmonary function in later childhood. There
may be, however, other exposures that may help protect against asthma or wheezing illness. These
include maternal intake of probiotics during pregnancy, higher birth order, and exposure to dogs and cats
during the first year of life.
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A review of possible relevant mechanisms implicates immune-mediated processes and epigenetics. For
example, multiple studies have shown that cytokine levels differ at birth among those children who may
be more likely to develop allergy and wheeze. There also is evidence that the fetus can generate an
independent immune response to proteins or allergens that the mother experiences in pregnancy.
Epigenetic changes refer to those that influence gene expression without any change in the DNA
sequence. They may influence gene expression differentially throughout a lifespan. In conclusion,
prenatal and early postnatal exposures do impact risk for later asthma, but more cohort-driven
mechanistic research must be done.
The Center for Childhood Asthma in the Urban Environment
Elizabeth Matsui, Johns Hopkins Hospital
Dr. Matsui, co-investigator for the Center for Childhood Asthma in the Urban Environment, provided
results of some of the Center's studies. The Center conducted studies of indoor pollutants and asthma in
Baltimore row homes. Preliminary data showed no differences between asthmatic children and controls
and no differences in levels of other common allergens. Because mouse allergen levels were higher in
these homes than in other cities, the researchers investigated whether the allergens were responsible for
asthma morbidity among children with asthma who were also mouse sensitized; the results were striking.
Across a multitude of asthma outcomes, there was a significant increase in asthma symptoms in children
who were mouse sensitized and highly exposed. The findings of this study are an important reminder to
conduct community or regional studies in addition to multicenter studies because local signals can be lost
when combining data from different regions. The researchers examined indoor pollutants in children's
bedrooms; although children with asthma had similar levels of exposure as control children, the causality
of environmental exposure to asthma development cannot be ruled out because prevalence rates of asthma
in this population were between 25 and 30 percent. In addition, the researchers have not conducted studies
of the same asthmatic children in different environments. Surprisingly, indoor pollutant levels are much
higher than outdoor levels, and the indoor exposure is likely to play a critical role in the development of
asthma, which is compounded by the fact that children today spend more time indoors than outdoors. The
researchers also looked at indoor particulate matter (PM) exposure in relation to poorer outcomes in
children with asthma and found a strong signal for coarse PM. Coarse PM fraction in bedrooms increased
risk in the number of days of symptoms and beta agonist use in children. There were some signals with
fine PM also, but results were not as consistent as results with coarse PM.
Clinical Experience with the Environmental Management of Asthma
and the NAEPP Expert Report 2007
James M. Seltzer, University of California at Irvine
Dr. Seltzer presented an overview of his experiences as an allergist/immunologist caring for children with
asthma and as a PEHSU Director, who must respond to inquiries from families regarding symptoms and
the role of environmental factors in allergy and asthma. As a clinician, he sees patients with
environmentally induced illnesses, including asthma, and other allergic disorders. The role of
environmental factors as precipitants of allergic disease is not always obvious, especially in children
under 5 years of age or where allergens are only one of several types of exacerbating factors. This applies
not only to the primary care doctor, but also to the allergist/immunologist who possesses particular
expertise in determining the spectrum of allergic sensitivity for a given patient. Allergy testing, especially
skin testing, can help identify potentially relevant allergens, whether or not they were suspected from the
medical history. Environmental factors can easily be missed and should be confirmed or ruled out in each
patient with the possibility of health problems that might be related to environmental exposures. As a
PEHSU Director, Dr. Seltzer responds to inquiries from parents, schools, the media, and other entities or
persons regarding environmental factors, and the questions typically are focused on high-profile
exposures, such as mold and diesel, but not other common exacerbants, such as dust mite or cockroaches.
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He discussed the significance of the assessment of environmental factors in each clinical case; the
importance of taking a careful, extensive history; determining if exposures are relevant; and, if relevant,
teaching the parent and child how to reduce exposure and to monitor future exposures and clinical
responses to exposure reduction. Reducing factors contributing to asthma severity can be accomplished
by environmental control measures for clinically relevant precipitants, such as reducing sources and
reservoirs of allergens and airway irritants in the child's environment. Dr. Seltzer also discussed the
hygiene hypothesis: early life exposures to certain allergens may provide protection from the
development of asthma and other allergic disorders later in life. Although early life exposure appears to
have more effect than exposure later, there are not enough data to recommend early exposure as a method
to reduce future risk. Education is important. Patients and physicians can learn how environmental factors
affect children's health, thereby improving recognition of these disorders as well as how to institute
effective environmental control measures. Finally, he outlined the goals of asthma therapy. For control of
asthma to be effective, it must be recognized, its nature defined, and the roles of all relevant
environmental factors identified and addressed for any given child. With successful environmental
control, pharmaceutical therapy and, if indicated, immunotherapy (desensitization), the need for clinician
intervention ultimately can be minimized. Lastly, to be effective, asthma therapy must be practical,
affordable, and convenient.
Discussion
A participant asked Dr. Matsui whether any composition studies have been done to identify PM.
The Johns Hopkins Children's Center had examined the composition of ambient PM previously, but
composition studies for indoor PM have yet to be performed. Animal particles, however, are much more
readily airborne than insect particles. It will be difficult to measure cockroach PM, because these larger
particles settle quickly and it is difficult to disrupt the dust to become airborne. The other session speakers
contributed to the discussion in regard to outdoor air pollution, including pollen, mold, traffic emissions,
and ozone, and all agreed that individual sensitivities and time of day need to be considered. Ozone levels
generally are highest during middle to late afternoon, and some outdoor molds sporulate at different times
of the day. Additionally, there is difficulty separating the effects of indoor pollutants from the effects of
outdoor air pollutants. Often, allergen and irritant concentrations are higher indoors. The complexity of
allergen and pollutant exposures, which occur in both indoor and outdoor environments, combined with
individual differences in susceptibility to these exposures, makes it challenging to provide guidance
regarding optimal environmental control measures to patients. In fact, recommendations in the new
NAEPP guidelines are more general than specific for this very reason. It was mentioned that the
guidelines are directed at the delivery of asthma care and what clinicians should do when interacting with
and educating the patient. EPA regulations affect outdoor triggers but do not regulate indoor exposures,
so patients who are advised to reduce particular indoor exposures are responsible for implementing the
environmental control practices. For those who are not homeowners, appealing to landlords to make
necessary modifications to the home or provide pest extermination is needed. Regarding outdoor exposure
to pollutants, ORD is examining school sites and athletic fields near roadways to better understand this
issue. A session speaker invited participants to become actively engaged in the process of updating the
guidelines, because the guidelines are posted for public comment during development.
A participant asked Dr. Miller for clarification of her lab's work on inhaled allergen and diesel exposure
on DNA methylation and immunoglobulin E (IgE) production in mice. The question was whether the
exposures in her studies were mixed or single. Dr. Miller responded that the effects on DNA methylation
and IgE production in mice were measured after combined exposures to the mold Aspergillus and diesel
administered chronically by inhalation over 3 weeks.
A participant asked Dr. Seltzer whether there is a lower boundary for which to diagnose asthma in
children and what the place of skin testing is in immunotherapy. Dr. Seltzer responded that the diagnosis
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of asthma in a 1- or 2-year-old is problematic, because young children typically have recurring episodes
of wheezing with viral infections. Children in families where other members have asthma or allergic
disorders are at increased risk of developing asthma or recurring reactive airway disease. Although these
and other risk factors can be identified, in a given child it is more a function of how often symptoms
occur, what they are associated with, and how persistent they are that helps to make the diagnosis. Among
1- and 2-year-olds, although a wheezing child may have asthma, the clinician must be concerned about
other diagnoses associated with recurring wheeze as well. Treatment usually involves a therapeutic trial
of bronchodilator, with or without inhaled steroids delivered by nebulizer or a pediatric mask attached to
a spacer, depending upon age and ability of the child to use a spacer. As far as skin testing, Dr. Seltzer has
tested down to 6 months. Typically, there is less skin reactivity and less IgE in younger children, but
testing can be performed at any time, even at birth.
SESSION IV: EARLY LIFE EXPOSURES TO METALS AND NEUROTOXIC OUTCOMES
Co-Chairs: Isaac Pessah, University of California at Davis, and Nigel Fields, U.S. EPA
Neurodevelopment, Autism, and Mercury: Biomarkers and Epidemiologic Approaches
Irva Hertz-Piciotto, University of California at Davis
Dr. Hertz-Piciotto discussed mercury and its relation to neurodevelopment and autism. The effects of
mercury are complex, but it is known to cause developmental delays and deficits in the mental, muscular,
visual/spatial, social, and sensory domains. Autism is a pervasive developmental disorder characterized
by deficits in three domains: (1) social interaction, manifested in lack of eye contact, lack of response to
name, failure to engage in joint attention, and so forth; (2) communications/language, including lack of
language or odd use of language; and (3) repetitive behaviors or restricted interests. The current
prevalence estimate of autism is about 1 case in 150 individuals and the ratio of males to females is 4:1.
There is a strong genetic component to autism, but environment also may play a role. Autism is a
multifactorial condition with a wide severity curve, yielding high-functioning individuals and individuals
who cannot function independently. Historically, autism was thought to be a result of poor parenting. It
now is generally accepted that it is a neuropathologic condition, but this legacy has led to a general
mistrust of the medical community by parent and advocacy communities. Brain imaging studies have
shown that facial recognition processing is one of the most affected areas and a hallmark of the condition.
When looking at faces, areas of the brain that are used in typically developing individuals are much less
activated in autistic individuals, and there is no one area of the brain that is affected by autism. Lesions
from autopsies are very widespread; this suggests that the insults occur very early in development, most
likely during gestation. The most replicated finding anatomically is the loss of Purkinje cells.
In the 1950s and 1970s, several high-profile mercury contamination episodes led to mass poisonings in
Iraq and Minamata Bay. Children exposed in utero appeared to be the most vulnerable. Severe
impairments, deficits, seizures, abnormal neuronal migration, and disorganized cerebral cortex were seen
in some autopsies. Studies followed birth cohorts in communities with high fish consumption. More than
1,000 mother-child pairs in the Faroe Islands were used to relate development to prenatal exposure, which
was measured through maternal hair, cord blood, and cord tissue levels. The results showed deficits in
attention, language, memory, and visual/special domains in children at 7 years. Similar findings and
motor deficits were evident at age 14. The Seychelles Islands study found no deficits, and it has been
difficult to reconcile the conflicting findings. Project VIVA (Venue-Intensive Vaccines for Adults), which
involved maternal hair mercury measurements, controlled for the benefits of fish consumption. Results
clearly showed the benefits of fish consumption, and harm from mercury was measured in a dose-
response fashion. Dental amalgams are a source of an inorganic form of mercury, which is broken down
into the methylated form and travels more easily across the blood-brain barrier. A randomized study
examining children who received mercury amalgams found no mental deficits, suggesting that
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susceptibility to mercury neurodevelopmental toxicity may be greater when exposure occurs prenatally as
compared with mid-childhood.
Studies regarding the link between mercury and autism are mixed and controversial. Several studies were
conducted on thimerasol, a vaccine preservative introduced in the 1930s. Thimerasol breaks down into
ethyl mercury and thiosalicylate. It was removed from many child vaccines in 2002 but remains in some
vaccines (e.g., hepatitis B virus and influenza). Most studies examining the link between thimerasol and
autism have been in the form of ecologic studies comparing before and after removal or introduction.
Very few studies have individual data, and multiple factors related to better diagnosis make the data
difficult to interpret. Vaccines, however, are not the only source of mercury. Home sources can include
nasal sprays, contact lens solutions, ear wax removal products, damaged batteries and light bulbs, and
skin lightening creams.
Dr. Hertz-Piciotto ended her discussion by presenting an overview of the Childhood Autism Risks from
Genetics and the Environment (CHARGE) Study, which is examining the causes and contributing factors
of childhood autism risk and the mechanisms of susceptibility, including those that are genomic,
immunologic, and metabolic. Many possible mechanisms may affect neuronal maturation, regulatory
genes, immune signaling, and endocrine processes. She discussed the catchment area, assessment
measures, study design and laboratory methods, and some preliminary results. A multiple linear
regression model was used to predict blood mercury. Preliminary findings showed that fish consumption
is predictive of mercury, and the use of nasal spray or ear wax removers or amalgam fillings was
associated with blood mercury level. There were no associations found with autism.
Future work will include multivariate analyses on baby hair locks, 483 newborn blood spots, and
mothers' hair that may represent the prenatal period. Other subsets will be analyzed regarding the
heterogeneity, metabolizing genes, and xenobiotics that may affect the immune system.
Genetic and Social Modifiers in Environmental Neuroepidemiology: The Role of Context in
Chemical Exposure
Robert Wright, Harvard School of Public Health
Dr. Wright discussed the variance found in studies of chemical exposure and health outcomes and
possible explanations for the different susceptibilities to certain neurotoxicants. A broad biological
framework for the reasons children are more biologically susceptible was presented. Fundamentally,
because the CNS is developing, there is ongoing activity (largely absent in adults) on generating cells,
differentiating cells, and cell migration. Finally, those processes that determine synaptic architecture and
the ability to develop acquired memory are dominant during early childhood. Environmental stimuli drive
whether a given synapse is kept or regresses. This is a form of natural selection and mimics evolution.
Synapses that serve an adaptive purpose are preferentially kept, and those that do not, regress.
Environmental chemicals may interrupt these processes and send them down different developmental
pathways. For example, at low doses, lead causes neurons to fire in a stochastic fashion, thereby
mimicking inappropriate environmental stimuli and the natural process of natural selection for synapses.
Over time, the resulting underlying synaptic architecture with prolonged exposure to toxic chemicals will
be less efficient. Like chemicals, social factors can be either maladaptive or adaptive. Neurohormones
such as cortisol are critical to synaptogenesis, and their metabolism changes in response to chronic stress.
Chronic stress, which is a nonchemical toxicant, is known to impair memory and learning capacity.
Because both chronic stress and lead share properties that can modify synaptogenesis, the joint or
sequential presence of lead and stress can be interactive. If instead of being stressful, social factors are
adaptive, animal studies demonstrate they will mitigate the effects of lead. On the other hand, if they are
maladaptive (i.e., produce stress), they may increase its toxicity. There may be ways to treat lead toxicity
beyond chelation. In animal studies, an enriched environment appears to mitigate the effects of lead
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poisoning. Following lead poisoning, animals that are socialized perform better than those in isolation
(stress environment). Self-esteem also may modify the effect of lead, as indicated by the results of one
human study. Maternal self-esteem is not stress, but it may be considered a buffer to chronic stress.
Mothers with higher self-esteem develop adaptive responses to chronic stress. Another pilot study in
humans showed that teens exposed to prenatal tobacco smoke and high levels of exposure to violence as
children (i.e., neurotoxicant and stressor) had worse performance on the Wisconsin Card Sorting Test
than teens with high tobacco smoke exposure and low violence exposure.
Genes also regulate synaptic formation. The process of synaptogenesis and synaptic pruning is an
interplay between genetics and the environment. At least three studies demonstrate that variants in the
apoE4 gene, which is critical to synaptogenesis, are associated with better cognitive performance.
Further, results suggest that the apoE4 gene variant might have a protective effect against lead. Blood
manganese also may be a predictor of neurodevelopment, and there is some evidence that manganese is
neurotoxic. Just as exposure does not occur in a social vacuum, it does not occur in a chemical vacuum.
Some people exposed to lead also are exposed to other chemicals. Animal studies show that joint
exposure is more neurotoxic than individual exposure to either lead or manganese, and human studies are
being conducted to address this finding as well.
Ongoing work in Mexico City will examine a birth cohort, in terms of metal mixtures and
neurodevelopment and also, with respect to stress as a modifier of lead poisoning, iron-deficiency anemia.
The studies will measure prenatal and postnatal contributions, genetic susceptibility, mixtures of metals,
and social modifiers and toxicity. The long-term goals are to identify those factors that increase or
decrease metal toxicity, understand the biology of metal toxicity to prevent toxicity, and treat toxicity
after it has occurred.
Criminal Behavior as a Late Outcome of Early Exposure to Environmental Lead
Kim Dietrich, University of Cincinnati
Data from previous cross-sectional and ecological studies suggest that there is an association between
exposure to lead and antisocial behaviors, including delinquency and adult criminality, and data from the
Cincinnati Lead Study show an association between prenatal and postnatal exposure and delinquent and
criminal behavior. Lead exposure associated with a higher risk for engaging in criminal activity is not a
new observation, but it is one that has resurfaced with some recent epidemiological studies. One 1996
study examined bone lead levels and the relationship of child scores on the Achenbach Child Behavior
Checklist. Clinically significant high scores on delinquency, aggression, and attention problems were
measured in those with high bone lead levels. An observational ecological study examined the correlation
between homicide rates and air lead contamination levels in more than 3,000 counties in the United States
and found a four-fold increase in homicide in counties with the highest rates of air lead concentrations.
Another study reported a statistically significant relationship between trends in sales of leaded gasoline
and violent crimes. Strong causal inferences cannot be made with ecological studies, but the results of
these studies are very suggestive. Although there are limitations, these pioneering studies clearly suggest
an association between environmental lead exposure in childhood and development of behavioral
problems.
The Cincinnati Lead Study, funded by NIEHS since 1979, is a prospective longitudinal study that
examines early and late effects of childhood lead exposure on growth, development, and neurobehavioral
outcomes. There are many lead paint residues in the catchment area of this cohort study, and the
researchers have a dense collection of blood lead determinations. Blood is collected prenatally and every
3 months through the first 6-7 years of life. From questionnaire data from study adolescents, there was a
statistically significant relationship in terms of the number of total reported delinquent behaviors with
respect to their blood lead levels. To determine relationships of early exposure to lead and adult
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criminality, criminal arrest records from the State of Ohio were used. Prenatal and 6-year blood lead
levels were significantly associated with total arrests, particularly for violent offenses. Lead increases
antisocial behavior through the direct route; it affects brain systems that are important in regulating
control. Gene-environment interactions also may play a role. It affects behavior through an indirect route
as well. Early lead exposure is associated with high rates of school failure and reading disabilities, and
children who perform poorly in school are more likely to engage in delinquent and criminal activities.
Volumetric magnetic resonance imaging was used to examine the brains of study participants. When
looking at the relationship between blood lead levels in these subjects, there was a significant association
to gray matter loss in the frontal regions of the brain (i.e., those areas that are involved in attention,
executive function, and regulation of social behaviors).
Discussion
A participant asked Dr. Dietrich about separate effects of blood lead at various ages to identify particular
ages that are more important, higher late blood levels as an indicator of sustained exposure, and the
temporal relation across the lifespan. Dr. Dietrich responded that the Cincinnati study did not address
critical periods, but there are many intra-individual tracking data. Blood lead levels remained fairly
consistent over the lifespan. When examining intra-individual blood lead levels in relation to IQ,
measures of executive function, and criminality, the later the blood lead, the more robust the parameter
estimate was in relationship to late outcomes. The higher late blood levels measured could be an
accumulated effect, but genetic factors related to excretion or retention of lead in the blood may be
involved.
A participant asked Dr. Hertz-Piciotto what advice she gives parents regarding consumption of fish.
Dr. Hertz-Piciotto replied that communication is the key issue with respect to complicated messages.
There is much variability across fish species, and not all fish have mercury. Several papers show that
many fish species do not have high mercury, so it is best to emphasize consumption of low-mercury fish;
consuming no fish is counterproductive because of the benefits of fish consumption, including during
pregnancy.
A participant asked Dr. Hertz-Piciotto if her research collaborators have observed any co-morbidities
between immune responses, mental disorders, and autism spectrum disorders. The participant asked for
comment on the biological pathways by which environmental triggers may be causing some susceptibility
to immunological responses and mental disorders or whether the environmental triggers are triggering
immune responses that causes brain development to go awry, thus exhibiting the phenotype of autism
spectrum disorders. Dr. Hertz-Piciotto replied that, in regard to co-morbidities, the research team is
examining fatty acid screens in children in the CHARGE Study, and one of the findings is that certain
fatty acids appear to be related to disorders that may be dysregulating. There may be a pathway where
there is an accumulation of long-chain fatty acids that are not being metabolized to the shorter chain down
the pathway. The team also is attempting to identify additional clinical signs of these disorders because
they are not always present, indicating that there may be subclinical issues in a subset of the autism cases.
One of the intriguing findings is of mothers of children with autism who make antibodies to fetal brain
tissue. The CHARGE Study is being followed up by a prospective study called the MARBLES Study,
which stands for Markers of Autism Risk in Babies—Learning Early Signs. Mothers of autistic children
are being recruited during or before subsequent pregnancies. Regarding the question of biology versus
environmental factors, all researchers would like to have insight on this issue.
A participant asked Dr. Wright about environmental treatment in humans, the current marker for stress in
his cohort, and chemical water pollution and exposure assessment. Dr. Wright explained that he is not
aware of any prospective human studies measuring whether the environment changes outcomes, but
cross-sectional studies have been conducted that examine whether the social environment modifies
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toxicity of lead or other neurotoxins. Because the brain is developing, there is no reason to think that an
insult that occurs at age 2 necessarily has to be permanent. His study is utilizing a variety of
questionnaires to assess stress that examine exposure to violence, negative life events, and perceived
stress measured longitudinally. He also is collecting biological markers of stress, such as salivary cortisol.
By collecting it multiple times over a random day, the diurnal rhythm of mothers during pregnancy and
their children at age 2 can be measured. The NCS also is measuring salivary cortisol at various time
points throughout the day in addition to collecting questionnaire data. Regarding water pollution, not all
forms of lead are bioavailable today but may become bioavailable in the future; therefore, a critical issue
in preparing long-term management plans at contaminated sites, particularly mining sites contaminated
with the relatively inert lead sulfide, is to ensure that nonbioavailables remain so. As an example of what
may develop, he cited the tragedy in Bangladesh in the 1980s. To counter the effects of a diarrhea
epidemic, shallow wells were dug for cleaner drinking water. But the digging changed the reducing
conditions in the soil so that the nonbioavailable form of arsenic in the soil changed to a bioavailable
form, which was dispersed in the ground water and poisoned the population. Land and the environment
may be stagnant, but human activity may change the bioavailability of chemicals.
OCTOBER 12,2007
SESSION V: TRANSPORTATION, THE BUILT ENVIRONMENT, AND CHILDREN'S HEALTH
Moderator: Joanne Rodman, U.S. EPA
Development Patterns and Children's Health
Tim Torma, U.S. EPA
Mr. Torma presented background on development patterns, health, and the implications of the built
environment. Contemporary community design has a tremendous impact on public health, particularly
children's health, and the environment. There have been three macro trends during the last 50 years:
(1) Employment and population growth heavily favored medium and large metropolitan regions versus
nonmetropolitan areas. (2) Within metropolitan regions, most growth has occurred in low-density
development at the fringe of urbanized areas. (3) There has been an emphasis on automobile travel at the
expense of other modes. During the past 20 years, vehicle travel increased as a result of how and where
populations are growing, not just because there are more people. Much has been known about this pattern
and its impacts on the environment for a long time. The health impacts of these trends, however, have not
been a focus of attention until recently.
The recent book Urban Sprawl and Public Health reveals that health outcomes are linked with land use
and community design, including air pollution and related illnesses; a decline in physical activity; obesity
and its attendant diseases; injuries related to auto dependence; threats to water quantity and quality;
mental illnesses; and erosion of social capital. The authors cited the precautionary principle, "When an
activity raises the cost of human health, precautionary measures should be taken even if some of the
causes are not scientifically proven." Another message from this book is that urban planners are public
health officials, whether they realize it or not. The public health community has been largely absent from
and now needs to engage in the conversation on built environment and development patterns because how
and where building occurs makes a difference.
Mr. Torma's presentation then focused on one particular aspect of the built environment—the size and
location of schools. In 1969, 48 percent of children walked to school; in 2002, that percentage dropped to
16 percent. Today, there are far fewer schools than in the 1930s, but more students. Schools are now
bigger, and these "mega-schools" are not accessible by foot. Many states have rules and policies that
mandate or favor large schools; some local districts have even banned walking and biking access, citing
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safety issues. Some argue that driving children to school protects them from predators, but the CDC
performed a study to determine barriers to walking to school and learned that distance, not "stranger
danger," was the main reason given by parents whose children did not walk to school. Many recently built
residential subdivisions have no sidewalks and are built as pods that require driving to arterial roads to
leave the neighborhood. There are multiple health implications as a result of the built environment in
general, and unwalkable schools in particular. For public health professionals, school siting decisions are
a logical place to start engaging on the built environment. Mr. Torma ended his presentation by
showcasing The Safe Routes to School Program and the "Regulatory Blueprint for Healthy Community
Design" handout.
Traffic, Trade, Air Pollution and Land Use Decisions
Andrea M. Hricko, University of Southern California
The Children's Environmental Health Center based at the University of Southern California has scientists
who study air pollution. The Center's Community Outreach and Translation Core is responsible for
translating science for the public, including policy-makers, and the Center's investigators testify
frequently in front of local, state, and federal elected officials.. They also serve on public scientific
committees and working groups at the local, state, and federal levels, with a focus on ensuring that the
research is delivered to the scientific, transportation, and urban planning committees as it relates to traffic,
trade, air pollution, and land use decisions. Studies by Center investigators show that children who live
within 500 meters of a freeway have a greater risk of reduced lung function than children who live further
away and that there is a greater probability of asthma in children who live close to busy roads. Local air
pollution exposure has adverse effects on children's lung function, independent of air quality measures.
Lung function at age 18 is 3-7 percent lower than expected for children living within 500 meters of a
freeway. Asthma prevalence is greater than 15 percent for children living within 50 meters of a busy road
their entire life, which is nearly double the prevalence for children living at least 200 meters away,
according to Center studies. Real estate developers need to be informed of these statistics and should be
encouraged to reconsider their development plans. School budget committees should be informed as well,
but conflict can occur with parents who would prefer to have their children go to a school in their own
neighborhood, even if it is situated close to a freeway, rather than have them be bused to another location.
Some California schools still are being built close to freeways, despite state guidelines and laws;
developers cite "overriding considerations" for not following these guidelines and laws. Another potential
conflict includes economics; land is very valuable in certain areas, and the only affordable land may be in
close proximity to freeways.
Ms. Hricko raised the following question: Should the Federal Highway Administration (FHWA) be
advising state transportation agencies to consider the latest research findings in their freeway expansion
decisions? Several years ago, EPA issued "hot spot rules" requiring mobile source air toxics analyses, but
currently FHWA states that it cannot validate the proximity-to-traffic studies and is waiting for an
upcoming Health Effects Institute evaluation.
Dr. Jonathan Samet, in a recent article in Inhalation Toxicology, suggests that: (1) control will require
both reduced emissions and increased separation of people from emissions; (2) there is a need for further
research to refine our understanding of the health consequences of traffic exposures (and as a basis for
formulating mitigation policies); and (3) a "no-regrets" strategy should be instituted to reduce exposures
while further evidence is obtained.
Ms. Hricko pointed out that the Los Angeles/Long Beach area is the epicenter for current international
trade and health debates in the United States. The volume of containers coming through West Coast ports
has increased dramatically since the 1970s (and U.S. ports have increased their international trade), and
imports continue to grow. Los Angeles ports are the gateway for 40 percent of U.S. imported products
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today, and imports through these two ports are expected to double or triple by 2030. California suffers the
air and noise pollution and damage to infrastructure, while the rest of country benefits from inexpensive
goods. The environmental impacts, however, also travel with the goods. Ships (with unregulated air
emissions) bring millions of imported containers into California ports, which adds to regional pollution.
Each container then becomes a truck on the freeway or is placed onto a train. Train and truck traffic
creates local problems in communities throughout the country because rail yards often are located in
immediate proximity to homes and schools, increasing the risk of health effects. Traffic, noise, and diesel
pollution increase, and the sense of community is decreased. In California, Ms. Hricko pointed out, the
proposed solution to the current congestion is to expand the infrastructure to accommodate three times as
much cargo and trucks by 2030. California elected officials, government staff, and leaders in the
transportation industry argue that expanding freeway infrastructure will reduce congestion and improve
air quality. California bond money for infrastructure projects include budgets for bridges, rail lines,
freeways, and possibly adding truck-only lanes to the 1-710 Freeway. The governor's current high-priority
projects are a new BNSF rail yard and an expanded Union Pacific rail yard located about 5 miles from the
ports in residential areas. Community, public health, and environmental groups argue that it would be
better to have rail yards at the ports so that containers are moved directly from ships to trains (and on to
the rest of the country), rather than to have rail yards in local communities, where residents and school
children have to breathe the diesel exhaust emanating from them.
Discussion
A participant asked about economic power as the driving consideration in the school development and
siting. Ms. FIricko responded that there is significant literature that disputes the claim of expected savings
of consolidated schooling. One study showed that costs are reduced in larger schools if costs are
measured per student year, but smaller schools are less expensive if cost per student who graduates is
measured; the issue is complicated. Often public policy dictates spending the money on a stadium in a
prime area versus building a school there. Segregation is another issue. How is building bigger schools
for integration addressed with well-intentioned public policy? Smaller neighborhoods and schools tend to
segregate. In the long term, however, economic desegregation needs to be included in public policy.
A participant asked about hot zones and the options for building schools elsewhere when a full 40 percent
of available land in Los Angeles may be adjacent to major roads and freeways. Ms. Hricko replied that
there are other studies that examine school construction and configurations and that look at siting parking
lots close to freeways, with the playgrounds and athletic fields farther away (to reduce exposure to
pollutants). Air filtration and air quality management are being tested as other considerations.
A participant commented on the complexity of planning. Ms. Hricko responded that when scientists,
physicians, and others in the public health community inject themselves into policy-making, a difference
can be made. It would be a great model for participants to return to their communities and resolve to go to
a zoning or planning meeting and offer health-based information in the planning process, said the
discussant. He asked session speakers to speak more about how these complexities could be incorporated
into practice. Mr. Torma explained that more reports and research are needed to provide evidence for
take-home messages at these planning meetings, but he believes that attending these meetings with
questions and concerns can be more effective than trying to provide all the answers. Merely mentioning
health issues increases considerations from everyone involved in the planning process; the public health
community needs to raise the questions. Another participant suggested developing a fact sheet of
obstacles from the health care professional standpoint and including possible solutions to those obstacles.
Participants can bring these fact sheets with them to the zoning meetings as a more effective contribution.
A participant commented about the fear factor in parents, with regard to children walking to school.
"Stranger danger" needs to be factored into the equation, whether it is substantiated by the statistics or
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not. Researchers must be proactive in obtaining and translating these data in a public forum when
discussing school sitings.
One participant asked about cost considerations with building new schools versus updating old ones.
Adaptive reuse is a great method to manage this issue, especially for buildings that were built in the 1920s
and 1930s and stand for civic pride. Some of these schools are being turned into lofts instead of being
demolished, but, if possible, the participant suggested, they should be kept as schools. There is a great
amount of literature showing the relative costs of renovating versus replacement. It often is not cheaper to
build new, but to bring the existing schools up to standards, depending on the age and condition of the
schools. Private schools may be more amenable to some of these arguments because they operate under a
different set of constraints and drivers.
A participant asked how lifestyle choices are considered when parents have a host of arguments against
walking to school, including time. Mr. Torma agreed that time is an issue, but people need opportunities
to engage their children; parents could be encouraged to walk their children to school and engage them in
discussions along the way. It is about prioritizing and interacting with children in a manner that does not
occur when driving them or spending time with them at night. A participant suggested that the global
warming issue is beginning to encourage thinking about these issues.
A participant asked about replacing diesel engines in school buses and if that will change the proximity
issue. A session speaker responded that there are attempts in many cities to replace diesel buses with
cleaner fuel, although it may take some time to replace all of the diesel buses. The EPA Clean School Bus
USA Web Site can be found at http://www.epa.gov/cleanschoolbus.
THE NATIONAL CHILDREN'S STUDY: ADJUNCT STUDIES
Marion J. Balsam, NIH
The NCS is an interagency, interactive study led by NICHD in partnership with CDC, EPA, and NIEHS.
It was authorized by the Children's Health Act of 2000 to study the effect of the environment on child
health and development. Environments to be studied include chemical, physical, biological, and
psychosocial. Gene-environment interaction is an important aspect of the study. The sample will include
100,000 children from across the United States from before conception through age 21. The goal is to
determine which environmental effects on children are harmful, harmless, or helpful. Another goal is to
find preventable causes of health-related conditions and provide evidence-based data to guide children's
health care, as well as health-related policy. Participants will be drawn from 105 sites across the country,
and 40 Study Centers will perform the research. The priority is to determine environmental exposures
(physical, chemical, biological, psychosocial) and their effects on specific outcomes. Priority outcome
areas include: pregnancy outcomes, neurodevelopment and behavior, injury, asthma, obesity, physical
development, and specific illnesses and disorders. Results from the core study are expected to spawn
further research with different research questions.
Adjunct studies will draw upon a subset of the parent study participants and/or their biospecimens or
environmental samples. These will be modular-focused studies, utilizing NCS infrastructure and samples.
Anyone with a good idea can initiate adjunct studies. Specifically, it is expected that many adjunct studies
will be initiated by government scientists or study center scientists. Independent researchers, research
advocates, and industry can initiate adjunct studies as well. The focus of these studies can be about any
topic, but there will need to be some mutual benefit to their leveraging the NCS. The adjunct studies will
rely on outside funding, not on the core NCS funding source. Reviewers evaluating proposals for adjunct
studies will rate such factors as scientific value to the NCS, public health importance, and proper fit with
the NCS. Also considered will be the burden on participants regarding time or discomfort, the burden on
the study infrastructure and logistics, human subject issues for any ethical or legal considerations,
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appropriate institutional review board (IRB) review, and proof of funding. A brief electronic preliminary
application is required. After the preliminary application is approved, a full application will be available
for submission. The review process is aimed at facilitating the timely review of proposals. The NCS
currently is expected to start in July 2008, which is the onset of a 1-year, Vanguard Center pilot year. The
full national study will begin with enrollment 1 year later. Adjunct studies can begin with the full study.
Proposals regarding preconception, delivery, and early infancy could be submitted soon. Opportunities
will continue to arise for additional research by leveraging the NCS, and adjunct studies will broaden and
enhance the NCS contribution to children's environmental health. More information can be found on the
NCS Web site at http://www.nationalchildrensstudy.gov.
Discussion
A participant asked whether funding is required prior to applying for adjunct studies. Dr. Balsam replied
that funding is not required, but the application asks about funding plans. After preliminary approval for
adjunct studies pending IRB decisions and so forth, the studies can obtain funding.
A participant asked whether there will be an opportunity to develop gene expression analysis and arrays
from the NCS. Dr. Balsam responded that the core protocol is very broad and will include specimen
samples and questionnaires. The NCS will be obtaining, storing, and analyzing the specimens, and the
data will be made publicly available. The research plan is available on the Web site now, so if others are
planning to do similar studies, they may not want to repeat efforts. The protocol draft is not very specific
about what gene expression analyses are planned, so if participants have specific questions, they can be
submitted by e-mail to ncs@mail.nih.gov.
A participant asked about the funding status of the NCS. Dr. Balsam answered that the NCS is funded for
Fiscal Year (FY) 2007 and anticipates funding for FY 2008. NCS is funded yearly.
A participant asked about the process for obtaining existing data and whether it will be similar to
NHANES. Dr. Balsam replied that the policy and procedures dealing with data access currently are being
developed.
A participant asked whether any of the people involved with the data warehousing for NHANES also are
involved with the NCS. Dr. Balsam replied yes, the CDC is involved with sampling, information
management, and laboratory and repository aspects.
A participant asked whether local sites have to wait for national data or whether access is available at the
local level prior to full data. Dr. Balsam responded that data distribution currently is being developed.
The NCS anticipates, however, that first access will be to government, followed by study centers, adjunct
studies, and then public use. When communities can have access is part of the process being developed
now.
SESSION VI: CHILDREN'S PROTECTION IN THE AFTERMATH OF A NATURAL
DISASTER: TOOLS FOR RECOVERY AND COMMUNICATING RISKS
Chair: Debra Cherry, University of Texas Health Center at Tyler
Dr. Cherry opened the session with a brief overview of the topic: tools for recovery and communicating
risks after hurricanes. The objectives of this panel were to describe the collaborative PEHSU response to
Hurricanes Katrina and Rita, provide experience and feedback from a Gulf Coast pediatrician at ground
zero, and describe the NIEHS Hurricane Response Portal. Hurricane Katrina was one of the most
devastating natural calamities to affect the United States. More than 354,000 Gulf Coast homes were
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destroyed; more than 200 sewage treatment plants and 140 oil and gas platforms were damaged; and
multiple health risks increased as a result of rampant mold growth, mountains of debris, widespread
demolition and reconstruction projects, and through exposure to toxicants in temporary housing. The
Tyler, Texas, PEHSU was the closest Center to ground zero and was called to help with communication
issues. The project involved multidisciplinary collaboration, and cleanup required the expertise of
scientists, engineers, volunteers, health care workers, and safety training professionals.
The potential hazards included returning to home sites too soon, sludge, structural damage, and lack of
respiratory protection. Joint documents and recommendations for dealing with environmental issues and
returning children to previously flooded areas were created and distributed to officials and parents. The
Center also answered calls from parents through atoll-free line.
Tales from Ground Zero: Hurricane Katrina and Pediatric Environmental Health in
Coastal Mississippi
Scott Needle, Formerly of Bay St. Louis Pediatrics
Dr. Needle joined the workshop by telephone to share his experiences with the aftermath of Hurricane
Katrina, including the logistical issues, the health effects, and the communication issues that he
encountered, particularly as they related to the formaldehyde problem in Federal Emergency Management
(FEMA) trailers.
He was in private practice in Bay St. Louis, Mississippi, when the hurricane made landfall. Between 50
and 90 percent of the local housing was damaged or destroyed, including his office and other public
health spaces. Although the medical community was prepared for some of the expected problems, they
did not anticipate the mental health issues that occurred including short-term memory problems,
confusion, and disorganization. Trauma was anticipated but not chronic stress.
The Sierra Club found significantly elevated levels of formaldehyde in one FEMA trailer, which led to
the finding that 29 of 30 trailers had elevated levels. Formaldehyde is a known respiratory irritant and is
classified as a carcinogen; it was found in the particle board in the trailers. The manufacturers voluntarily
had taken it out years before, but the boards were still circulating. There are no government levels
regulating formaldehyde in travel trailers and no standard for levels of safety for children. Dr. Needle
noted that many families reported recurring respiratory problems in their children when they had been in
good health before staying in the trailers. FEMA explained that a small number of cases were being
monitored, and no major problems were anticipated. No government resources were available through the
summer of 2006 to analyze formaldehyde, but the Sierra Club still was finding elevated levels. In
February 2007, the media investigated the manufacturer of the trailers and discovered respiratory
problems with the factory workers and particle board sheets that were still wet with formaldehyde. In
May 2007, the CBS Evening News ran a story of results of the 2-month investigation, which prompted the
Department of Homeland Security to contact Dr. Needle to determine how best to study the issue. The
next month, the House Committee on Oversight and Government Reforms announced that they would
hold hearings and invited Dr. Needle to testify. FEMA workers testified that they had voiced
formaldehyde concerns about the trailers as early as March 2006. FEMA finally announced last month
that they are now taking steps to move people out of these trailers. But what about the families still living
in these trailers? The fundamental question remains unanswered: Is the formaldehyde the cause of the
health problems, and if not, what is? Researchers must work hard to find out. Almost every agency failed
to take ownership and responsibility for public health, and the CDC cannot just launch an investigation.
The providers on the ground are the ones providing public health the first few months following a natural
disaster. These providers rely on the experts for advice and need government agencies to listen to their
concerns. Will we be able to handle future problems that weren't anticipated?
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NIEHS Environmental Health Sciences Data Resource Portal
Marie Lynn Miranda, Duke University
Dr. Miranda presented satellite imagery of the New Orleans area from pre- and post-Hurricane Katrina
perspectives. These images showed the scale of persistent flooding in an expansive area to help gauge the
potential environmental health effects. The group was tasked with setting up work for the entire Gulf area,
not just New Orleans. The key health consequences questions that arose involved mold, respiratory
health, contaminant transfer, solid waste management, and mental health, and the NIEHS chose to
develop the Hurricane Response Web Portal to build and maintain an extensive data file and archive. This
archive allows many different environmental health questions to be examined and provides a
collaborative work space and working tools that allow people from all over the country to work together
on a long-term living resource. Data from the Web portal can be accessed directly from the NIEHS Web
Site. The portal is user friendly and provides maps and imagery, query tools, measurement tools, data
manipulation tools, potential contamination sources, water quality information, and sediment information.
There is free and open access to these data. She demonstrated examples of how to make specific queries
and how to download data by geographic and other variables and provided navigation instruction. A
customizable research environment and custom reports are available.
Discussion
A participant recommended a book called One Dead in Attic by Chris Rose for a more information about
how New Orleans has been coping since Hurricane Katrina.
KEYNOTE ADDRESS: THE NATIONAL FORUM ON CHILDREN AND NATURE
Speaker: Lawrence A. Selzer, The Conservation Fund
Introduction and Discussant: Howard Frumkin, CDC
Mr. Selzer explained that he wanted to challenge researchers to broaden their investigations to include the
health effects resulting from communing with nature. There is a growing body of evidence pointing to the
benefits of nature, but more data are needed to effect positive change with respect to children's health and
the environment. As the nation becomes more urban and the demographics continue to change,
reconnecting children to nature will be less about bringing them to nature and more about bringing nature
to them. Nature must be brought to children in a manner that makes sense to them. This requires a more
strategic vision of reconnecting children and nature; it is a mission that cuts across sector, status, and
geography. This is the challenge, and leadership is needed to succeed.
One in five American children is considered obese, and one in three with diabetes has the type II form; 25
years ago, doctors did not even have a name for it. Children in the United States now gain three to five
times more weight during the summer than they do during the school year. There are classes in urban
schools where as many as one-third of the boys are on Ritalin or similar medicines. Pediatricians do not
see as many broken bones anymore, and one of the most common ailments among children eight to 18
today is repetitive motion disorder. Fifty percent of Hispanic boys in this country drop out of school by
the eighth grade. Some states now project their future prison needs based on third grade reading scores. If
this trend continues, the first generation since World War II will exist that will have a shorter life span
than its parents. Sensationalist media coverage and fearful parents have scared children right out of the
woods while promoting a litigious culture of fear that favors safe, regimented sports over imaginative
play outdoors. This anxiety can feed on itself, and those who watch more television have more sense of
the potential dangers and less engagement with their community. The result is the perception that the
outside has become more dangerous and thus the freedom to explore and improvise is reduced
dramatically. The radius beyond which children are not allowed to roam has shrunk by 89 percent during
30
The Office of Research and Development's National Center for Environmental Research
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2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
the past 20 years. During the past 30 years, children of the digital age have become increasingly alienated
from the natural world with disturbing implications for their physical fitness, their long-term mental and
spiritual health, and the environment. Young people who grow up without spending time in nature are
much less likely to be strong champions for the environment when they reach voting age, thereby
jeopardizing the land legacy that the nation has spent the last 200 years setting aside.
Mr. Selzer provided an overview and history of The Conservation Fund, which has protected more than 6
million acres of America's outdoor areas during the past 21 years. Leadership and new ideas, resources,
partners, research, and data are needed urgently. Reconnecting children with nature is the passion of our
time. The National Forum on Children and Nature is a new initiative, a collaborative effort launched in
June. The 2-year effort is to identify and implement signature projects across America that serve to
reconnect children and nature. Individually and collectively they will be a most powerful form of
advocacy for change, for a new direction in the products that are made, the services that are delivered in
communities that are built, and the education that is provided. They will help to elevate this issue to the
highest levels of society so it becomes a national priority. Reconnecting children with nature cannot be
legislated or regulated; it must be done by changing the culture of the country and to do that we need to
better understand the connection between children, nature, and health.
Two examples are being pursued through the Forum. The first is in the area of technology. The world is
technological, so childrens' attraction to technology must be used to get them outdoors. One idea of the
National Forum is to work with a new organization called the Serious Games Initiative, which was
created by an independent group of game developers who view video games as an opportunity for social
good and achieving social purpose. A national competition to make state-of-the-art technology that has to
be played outdoors is being launched. The next example deals with the built environment, especially how
the environments are built where Americans will live tomorrow.
The modern America of obesity, inactivity, depression, and loss of community has occurred because of
legislation, subsidy, and planning. A subgroup of the National Forum consisting of some of the most
progressive developers in the country has been formed. This group is focusing on understanding children
and nature design elements, identifying best practices, and alternately arriving at a national certification
standard for child-friendly developments. This is the kind of energy that the National Forum is
channeling. The real value of the projects is the opportunity they provide to investigate what happens as a
result. This chance to gather primary data that will help to influence policy and practice across the country
must not be lost. Forum collaborators are building a solid component as part of each of these national
projects. They will conduct research on what happens as a result and make these data available.
Beyond the allure of technology, beyond the isolating design of new development, beyond the fear of
stranger danger, there is another fundamental issue that requires our immediate attention: the increasing
lack of places to be outdoors and the lack of leadership at the federal level to address this issue in a
meaningful way. America loses more than 3 million acres a year in development and sprawl. The current
administration has proposed twice to permanently terminate the Land and Water Conservation Fund, the
most powerful land protection program in this country. There also is a crisis in creativity. It is known that
protecting watersheds is one of the methods by which to assure clean, safe drinking water, so protecting
the sources of drinking water protects public health. It is known that air pollution contributes to
cardiovascular disease, respiratory disease, and allergies. Therefore, protecting air quality and land
protects public health.
Protecting natural landscapes is a powerful form of preventive medicine, but only 5 percent of the money
spent on health care in the United States is allocated to preventing disease and promoting health and a
healthy lifestyle. Nature needs to be viewed as the first prescription. People do not want less
environmental protection; they want smarter protection that balances economic and environmental
31
The Office of Research and Development's National Center for Environmental Research
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2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
objectives. It is this dynamic that is driving the tremendous force and support of the environment at the
state and local levels. More than 30 billion dollars in just the last 5 years in state and local bond money
were allocated by taxpayers to protect open spaces across the country, including natural areas and
neighborhood parks. Recent election results show that a wide variety of Americans care about these
issues. No one among us wants to be a member of the last generation to pass on to its children the joy of
playing in nature.
Discussion
A participant asked for clarification about bringing nature to the children versus taking them to nature.
Mr. Selzer responded that redefining what nature means (redesigning alleys to replace lost park land) is
part of this, but he cited a National Geographic Society program that brings children to national parks.
Children expressed fear of the dark, of quiet, and of nature. It was too foreign for them to continue
interest in it. Children must be moved along a continuum to help them identify what represents nature in
their own neighborhoods in a manner in which they can connect and continue with sustained investment.
This improves school performance and increases the number of students who continue to secondary
education; many of them have a lifelong interest in the natural world.
A participant asked about the issue of people who view nature as having a big backyard. Mr. Selzer
explained that people tend to show a preference for a house and big yard as a sign of success, comfort,
and quality of life. It is a cultural issue, but it has an ecological impact. It represents a loss of land and
loss of migration and native species. The human health impacts of those kinds of sprawling developments
have just begun to be understood. The impacts of changing those patterns of development must be
considered and documented through research. For example, only 30 percent of people who live on a golf
course play golf, but they all paid a higher premium to purchase the lots because they like the open green
space. Developers should build housing developments on open land and charge the higher premium but
they will not because it is an unfamiliar idea. Change must occur slowly, the success stories must be
highlighted, and the results documented to effect cultural change.
A participant commented about the disconnect that she has seen in some of the nature programs; most of
them failed or the children could describe the environment but could not see themselves in it. She asked
for a description of a better way to design these programs. Mr. Selzer explained that what it means to
experience nature must be redefined. Researchers need to come together and promote one curriculum on
environmental education, because there are too many competing factions. Obesity rates are rising, but
participation in structured sports is the highest it has even been; therefore, there is something about
unstructured time and play outdoors that matters. It has to do with engaging with nature first hand.
Environmental education must include being outside in a less structured way.
A participant described a recently convened a group of state and environmental directors that dealt with
the issue of how to collaborate on smart growth and asked what can be done in the early stages. Mr.
Selzer replied that all that can be achieved with legislation has been achieved, and now the power of the
marketplace is needed to drive things forward. The developers must be encouraged to change.
A participant suggested that participants should consider running for local office to make changes. If
researchers sit on local planning agencies or the school board, environmentalists and the local health
community will help fund the campaign. Mr. Selzer added that a recent study showed that children who
emerge as leaders in the gray playgrounds (blacktops) are the most physically mature. The children who
emerge as leaders in a green playground are the most creative. Green space is not needed in an urban
setting because sometimes it is not available; some schools put it on their roofs. He described a school of
the future in downtown Manhattan. Regarding running for office, the only thing protecting the land is the
will of the public officials; 20 years from now if the elected officials do not have a stake in the land, it is
32
The Office of Research and Development's National Center for Environmental Research
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2007 Children's Environmental Health Workshop: Discover, Treat, Prevent, Prepare
in jeopardy, which is why we need to engage children today because it takes a lifetime to build a
commitment like that.
A participant expressed a sense of personal frustration and lack of creativity and mentioned children who
are afraid to go outside because of drive-by shootings. Mr. Selzer agreed that one of the central issues is
safety. He described an initiative called America's Promise, started by Colin Powell. It is an umbrella
organization designed to improve the quality of the lives of the 30 million children who are most at risk in
the United States. One of the central directions is based on the concept of school as the center of
community. Many inner city schools are barren and lacking in programs. Maybe, school can be the place
where education takes place, not just in the classroom, and where children spend a lot more time. This
will take time, budget, policy, and creativity; and schools as the center of community is the direction in
which this program is headed.
Dr. Frumkin stated that now is the time to submit proposals through the National Forum on Children and
Nature. Information can be found at http://www.conservationfund.org/children_nature.
CLOSING REMARKS
William H. Sanders III, U.S. EPA
Mr. Sanders thanked the presenters and expressed his appreciation for their quality talks. He specially
thanked Mr. Fields and Dr. Frumkin, whose comments complemented the theme today of thinking in
broader terms. The community is at a point of opportunity to think more broadly about CEH to
demonstrate and measure the results. He thanked participants for engaging the speakers in each of the
sessions and thanked the planning committee and coordination teams for their efforts in bringing about
this workshop. Because this workshop was enlightening and a great opportunity to connect and discuss
ideas, another workshop may be planed in the future. He anticipates great response to this workshop.
Mr. Sanders adjourned the meeting at 12:30 p.m.
33
The Office of Research and Development's National Center for Environmental Research
-------
2007 Children's Environmental Health Workshop:
Discover, Treat, Prevent, Prepare
Hamilton Crowne Plaza
1001 14th Street, NW
Washington, DC
October 10-13, 2007
Final Participants List
Alicia Aalto
U.S. Environmental Protection Agency
Alan Abelsohn
University of Toronto
Mark Anderson
Denver Health
Bob Axelrad
U.S. Environmental Protection Agency
Daniel Axelrad
U.S. Environmental Protection Agency
Marion Balsam
National Institute of Child Health and Human
Development
Claire L. Barnett
Healthy Schools Network, Inc.
Elizabeth Bayne
ASPH Fellow
U.S. Environmental Protection Agency
Nancy Beaudet
University of Washington
Martha Berger
U.S. Environmental Protection Agency
Liz Blackburn
U.S. Environmental Protection Agency
Cindy Blasko
Magee-Womens Hospital
Joseph Brain
Harvard School of Public Health
Maggie Breville
U.S. Environmental Protection Agency
Margot Brown
ASPH Fellow
U.S. Environmental Protection Agency
Rebecca Brown
U.S. Environmental Protection Agency
Susan Buchanan
University of Illinois at Chicago
Elizabeth Buckley
Pesticide and Toxic Chemical News
Irena Buka
Misericordia Community Hospital
Richard Callan
U.S. Environmental Protection Agency
Kari Casas
University of Texas Health Center at Tyler
Stephanie Chalupka
University of Massachusetts Lowell
Debra Cherry
University of Texas Health Center at Tyler
Gwen Collman
National Institute of Environmental Health Sciences
Tina Maragousis Conley
U.S. Environmental Protection Agency
Nora Conlon
U.S. Environmental Protection Agency
Ted Coopwood
U.S. Environmental Protection Agency
Paula Davis
Association of Occupational and
Environmental Clinics
-------
Regina De La Cam pa
Canadian Institute of Child Health
Kacee Deener
U.S. Environmental Protection Agency
Dona DeLeon
U.S. Environmental Protection Agency
Kim Dietrich
University of Cincinnati College of Medicine
Darlene Dinkins
U.S. Environmental Protection Agency
Ruth Etzel
Southcentral Foundation
Cathey Falvo
International Society of Doctors
for the Environment
Elaine Faustman
University of Washington
Nigel Fields
U.S. Environmental Protection Agency
Michael Firestone
U.S. Environmental Protection Agency
Bettina Fletcher
U.S. Environmental Protection Agency
Brenda Foos
U.S. Environmental Protection Agency
Joel Forman
Mount Sinai School of Medicine
Larry Frisch
Northeastern Ohio Universities College of Medicine
John Furman
Washington Department of Labor and Industries
Maida P. Galvez
Mount Sinai School of Medicine
Wayne Garfinkel
U.S. Environmental Protection Agency
Robert Geller
Southeast Pediatric Environmental Health
Specialty Units
Suzanne Giroux
Children's Hospital Boston
Benjamin Gitterman
Mid-Atlantic Center for Children's Health and the
Environment
Rose Goldman
Cambridge Health Alliance
Lauren Gordon
ASPH Fellow
U.S. Environmental Protection Agency
Beth Graves
Environmental Council of the States
Kimberly A. Gray
National Institute of Environmental
Health Sciences
William Griffith
Center for Child Environmental Health Risk
Research
Kim Harley
University of California at Berkeley
Michael Hatcher
Agency for Toxic Substances and Disease Registry
Birgit Claus Henn
Harvard School of Public Health
Irva Hertz-Picciotto
University California at Davis
Bette Hileman
American Chemical Society
Mary Hilko
Rocky Mountain Poison and Drug Center
Marianne Hopkins
Harvard School of Public Health
Andrea M. Hricko
University of Southern California
Carolyn Hubbard
U.S. Environmental Protection Agency
Barbara Huggins
The University of Texas Health Center at Tyler
Cathy Hunt
Magee-Womens Hospital
Amaris Johnson
U.S. Environmental Protection Agency
-------
Catherine Karr
University of Washington
Matt Kirby
U.S. Environmental Protection Agency
Katherine Kirkland
Association of Occupational and Environmental
Clinics
Annette Kirshner
National Institute of Environmental Health Sciences
Susan Laessig
U.S. Environmental Protection Agency
Larry Lowry
The University of Texas Health Center at Tyler
Jenny Lu
Region V Pediatric Environmental Health
Specialty Unit
Edward Master
U.S. Environmental Protection Agency
Elizabeth Matsui
Johns Hopkins Hospital
Lisa Matthews
Environmental Council of the States
Pamela Maxson
Duke University
Ellen Mazo
Children's Hospital of Pittsburgh
Rob McConnell
University of Southern California
Leyla McCurdy
National Environmental Education Foundation
Regina Milbeck
U.S. Environmental Protection Agency
Mark Miller
University of California at San Francisco
Rachel L. Miller
Columbia Center for Children's Environmental
Health
Marie Lynn Miranda
Duke University
Veronica Monti
Argentine Society of Doctors for the Environment
Ann Naughton
Stroger Hospital
Scott Needle
Bay St. Louis Pediatrics
Tom Neltner
National Center for Healthy Housing
Aaron Niman
Southeast Pediatric Environmental Health
Specialty Units
Janice Nodvin
Southeast Pediatric Environmental Health
Specialty Units
Sunghee Oh
U.S. Environmental Protection Agency
Jerome Paulson
Mid-Atlantic Center for Children's Health and the
Environment
Devon Payne-Sturges
U.S. Environmental Protection Agency
Cindy Pellegrini
American Academy of Pediatrics
Frederica Perera
Columbia Center for Children's Environmental
Health
Damiris Perez
Mount Sinai School of Medicine
Timothy Phelan
University of Maryland School of Medicine
Pamela Rao
Farmworker Justice
Pat Rizzuto
BNA, Inc.
Joanne Rodman
U.S. Environmental Protection Agency
David Rowson
U.S. Environmental Protection Agency
Leslie Rubin
Southeast Pediatric Environmental Health
Specialty Units
William H. Sanders
U.S. Environmental Protection Agency
-------
Jessica Sapienza
National Institutes of Health
Adam Sarvana
Inside Washington Publishers
Sheela Sathyanarayana
University of Washington
Kenneth Schoendorf
Centers for Disease Control and Prevention
James Seltzer
University of California at Irvine
Lawrence A. Selzer
The Conservation Fund
Paula Selzer
U.S. Environmental Protection Agency
Katherine M. Shea
University of North Carolina
Perry Sheffield
Mount Sinai School of Medicine
Martha Shimkin
The Track Group
Adam Spanier
Cincinnati Children's Hospital Medical Center
Marian Stanley
American Chemistry Council
Laurie Stillman
Asthma Regional Council
Maryann Suero
U.S. Environmental Protection Agency
Oscar Tarrago
Agency for Toxic Substances and Disease Registry
Kevin Teichman
U.S. Environmental Protection Agency
Hugh Tilson
U.S. Environmental Protection Agency
Tim Torma
U.S. Environmental Protection Agency
Whitney Trulove-Cranor
U.S. Environmental Protection Agency
David Turcotte
University of Massachusetts Lowell
Maria Valenti
Greater Boston Physicians for Social Responsibility
Nita Vangeepuram
Mount Sinai School of Medicine
Mary Walker
The University of Kansas Medical Center
Teresa Walker
The University of Texas Health Center at Tyler
Jonathan Weinkle
Children's Hospital of Pittsburgh
Robin Whyatt
Columbia Center for Children's Environmental
Health
Stephen Wilson
University of Cincinnati
Mary Wolff
Mount Sinai School of Medicine
Alan Woolf
Children's Hospital Boston
Robert Wright
Harvard School of Public Health
Margo Young
U.S. Environmental Protection Agency
Contractor Support
Cerena Cantrell
The Scientific Consulting Group, Inc.
Patrice Pettinato
The Scientific Consulting Group, Inc.
-------
-------
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-------
Connecting Children and Nature
Tin' fSualln'Hiil K
-------
Climate
change:
Temperature
rise
Sea level
rise
Hydrologic
extremes
-------
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washingtonposl.com i
Climate Change Scenarios Scare, and Motivate,
Kids
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*fTAi"j ^dJJ? tttmmer, I got ttetply defrtsted about ow planet
i/ / ^iWnJf Aflw enough probltmt of my own.
Katrina Survivors'
Mental Health Problems From Kalrina Persist Psychiatric NeedS
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Breakdown?
-------
-------
Care for the
individual
patient Care for the
co mm unbare for
future
generations
-------
Evolution of Biomarkers for Pesticides:
Examples From the Agricultural Setting
Catherine Karr, MD, PhD
Director, Northwest PEHSU
Elaine Faustman, PhD
Director, Center for Child Environmental
Health Risks Research
University of Washington, Seattle, WA
Focus: Organophosphate Pesticides
Reason # 1: Widespread exposure
Recent decreases in home/garden use
(regulatory restrictions and phase outs
based on child health concerns)
Continue to be used heavily in agriculture
Focus: Organophosphate Pesticides
Reason # 2: Acute Toxicity
OP = pesticide type most often implicated in
symptomatic illness reported
PESTICIDES MOST OFTEN IMPLICATED IN SYMPTOMATIC
ILLNESSES. 1996
Organ iphcsphatas
Pyrethrins and pyrethroids' -
Pine oil disinfectants
HypnchlDrita disinf
Insect repellents
Phenol disinfectant;
Carbamate insecticides
Organcchlorine insecticides
Phenoxy herbicides
Anticoagulant radenticides
All Other Pesticides
Total all pesticide^disinfectant
in. |.i .1 small niiml." r "I • .rr^v.vith unknown fry-.
'' Rough estimate: include? some veterinary products not classified by chemcal typ
n '•! \'i'\''
-------
Biologically Early Altered
5rr BSLT r srr
Dose I Effect or Function
Clinical Setting Questions
A parent....
I just read the CDC report and I have
learned that my child may have pesticides
in her body - what does this mean? Do I
need to have my daughter tested?
A colleague....
I am sensitive to drug X, could this affect my
susceptibility to pesticide""
Public Health Sector Questions
Risk Assessment Questions
A public health officer in a rural community...
Should our healthy family fact sheet include a
recommendation for choosing organic foods?
Which populations are most vulnerable to potential
adverse health outcomes from pesticide exposure?
A federal agency leader....
Should we have a national medical monitoring program
tionally exposed agricultural workers?
A policy maker asks....
Has the change in regulation of diazinon and
chlorpyrifos reduced exposure in at risk
populations?
Should regulatory decision making incorporate
evaluation and protection of the most genetically
, _,, 1on?
Considerations for progress
Stage of validation/utility, limitations,
knowledge gaps
How to increase the clinical, public health
and risk assessment relevancy?
-------
Key Issues
Cholinesterase Testing:
Pediatric Clinical
Perspective
Catherine Karr MD PhD
University of Washington
RenionXPEHSU
Unique clinical diagnostic tool for acute pesticide
poisoning
Under recognition of OP poisoning in children
Kids present differently
Knowledge gap
Interpretation
T-individual variability
Cholinesterase Test
Biomarker of biologically active dose
Measures inhibition of Cholinesterase
enzyme using a blood sample
Plasma (pseudocholinesterase)
RBC (acetylcholinesterase)
Surrogate for acetylcholinesterase in the
nervous system
Cholinesterase Inhibitors Toxicity
Effect builds up over time and
the "Off Switch" gets stuck ON
Diaphoresis
Salivation
Lacrimation
Urination
Defecation
More likely to have hypotonia & mental status changes
such as lethargy and coma, seizures
eg. seizure occurrence based on case series:
adults 2-3%
children 22-25%
Less likely to have the classic hypersecretion, particularly
at initial presentation
Often mistaken for viral illness (respiratory infection,
-------
Under recognition of OP poisoning
in children
In one 1980s case series, the diagnosis was incorrect in 16
of 20 cases
In epidemic OP poisoning in midwest, southeast US,
missing and delayed diagnosis for months to years
No index of suspicion = no diagnosis
Training Gap
Health care providers in NW agricultural
setting caring for farmworker families
(2005)
Any previous training on pesticides &
health? 49%
Child specific info? 22%
NWPEHSU WebCME
Organophosphate Pesticides and Child Health: a
primer for health care providers
http://depts.washington.edu/opchild/
Diagnostic Testing
If suspect OP exposure
Red blood cell (acetylcholinesterase)
Plasma (pseudocholinesterase)
Certain OPS may selectively inhibit either
plasma or RBC acetylcholinesterase
Cholinesterase Activity Depression
Occurs w/in few minutes or hours
Effects on plasma enzyme generally persists
for several days to a few weeks.
The RBC enzyme activity may take several
days to reach its minimum and usually
remains depressed longer, sometimes 1-3
Cholinesterase Activity Depression:
Interpretation
Great variability in normal general population
baseline limits usefulness of reference range
Need to interpret in relation to individual's own
baseline - post exposure follow-up with same
lab and method
20% increase in plasma OR 15% increase in
RBC suggests clinically significant exposure
-------
Chronic Exposure Toxicity
Cholinesterase testing is limited to diagnosis
of clinically significant acute poisoning via
the cholinergic pathway
Neurodevelopmental toxicity may occur via
alternative mechanisms
Toxicological and epidemiological evidence
OP Pesticides & Developmental Toxicity:
Cholinergic-lndependent Mechanism
In vivo evidence (embryonic/neonatal rat models) and in vitro
models (neuronal rat cell lines)
Dosage biologically plausible, below amount needed to
effectively inhibit acetylcholinesterase
Effects seen throughout brain, including regions with little
cholinergic innervation
Cell loss & apoptosis seen i
Neural deficits appear in adc
after exposure
OP Pesticides & Developmental Toxicity:
Cholinergic-lndependent Mechanism
Several common signaling cascades shown to be effected that
are used in many developmental pathways
May help explain widespread & delayed-onset OP effects
during development
May explain observations in epidemiological cohort studies
Implications of Non-Cholinergic
Organophosphate Toxicity
Child OP exposure toxicity may result from
non-cholinergic endpoints
Clinical markers beyond Cholinesterase
testing
Beyond Cholinesterase testing
Development of clinical application of urinary
marker monitoring?
Confirm acute exposures?
Identify concerning chronic exposures?
Influence clinical decision-making?
Preventive guidance
-------
CMC Biomarker Faustman
Biomarkers of Pesticide Exposure: Lessons
for Children in Agricultural Communities
Biomarkers for Monitoring Exposure and
Effect in Populations
Elaine M. Faustman
Bill Griffith
Examples of Chemicals Applied to
Washington State Crops, 2001
Chemical class
crop
Chemical
Organophosphates Apples Azinphos-methyl
Chlorpyrifos
Phosmet
Potatoes Ethoprop
Metamidophos
N-Me Carbamates Apples carbaryl
Potatoes Aldicarb
Dithiocarbamate Apples Mancozeb
Potatoes Mancozeb
Pounds applied
241,000
234,000
138,000
119,000
143,000
202,000
153,000
82,000
343,000
Source: "Agricultural Chemical Usage (PCU-BB)" National Agricultural Statistics Service,
Agricultural Statistics Board, U.S. Department of Agriculture
(http://jan.mannlib.cornell.edu/reports/nassr/other/pcubbAccessed 05/03)
Agricultural Pesticides: Contributions of
Occupational Factors to Home Contamination
Metabolic Scheme for CP
Crt3A444lh#twic )
s>^*
CNMpynftM O.W*CP*nO*i>
Faustman et at. (2006)
Metabolites of Organophosphate
Pesticides
• Biomarkers of exposure
• Nonspecific Diakyl Phosphate
(DAP) metabolites
- Six DAP Metabolites
- Each metabolite can be
produced by multiple OPs
- Divided into two groups
• Dimethyl metabolites
- DMP, DMTP, DMDTP
• Diethyl metabolites
- DEP, DETP, DEDTP
• Specific metabolites
- Chlorpyrifos metabolites
• TCP, DEP, DETP
- Chlorpyrifos-methyl metabolites
• TCP, DMP, DMTP
-------
CMC Biomarker Faustman
Metabolites of Organophosphate
Pesticides
Selected OPs and DAP metabolites
Diethyl OPs
chlorpyrifos
diazinon
disulfoton
ethion
parathion
azinophos methyl
chlorpyrifos methyl
dichlorvos (DDVP)
malathion
methyl parathion
naled
phosmet
trichlorfon
DEDTP
DEDTP
DMDTP
DMDTP
DMDTP
DEP
DEP
DEP
DEP
DEP
DMP
DMP
DMP
DMP
DMP
DMP
DMP
DMP
DETP
DETP
DETP
DETP
DETP
DMTP
DMTP
DMTP
DMTP
DMTP
NHANES Data for DMTP in Urine
Random sample of US Population
Comparison across ages
in 2000-2001
Comparison for children
f6'11 Vears old) across
time
What do these values mean for my
Children?
Many Values Are Below
Limits of Detection
Child DETP
Quantiles of a log normal distribution
NHANES Compared to Farmworker Family
Data for DMTP in Urine
DMP in Adult Urine: QQ Plots to
Estimate Population Distribution
Group of 8 High'
Exposed
Individuals
Detection
Limit
-------
CMC Biomarker Faustman
Distribution of Adult DMTP from year 1:
Impact of Crop
Assessing Children's Pesticide Exposure
via the Take-home Pathway
Workplace
Adult Child
exposure exposure
Car dust
Urinary metabolites higher in adults who
worked in pome fruit and their children
Adult DMTP in Urine
8
*~ Non-Pome
Fruit
Pome
Fruit
Child DMTP in Urine
3
Non-Pome
D Fruit
O
Pome
D Fruit
10 100 1000 1 10
Urinary DMTP |jg/liter
100 1000
Coronado et al., Env. Hlth. Persp., 2004,
Two longitudinal studies of OP metabolites
used to estimate within and between variability
• Multiple measurements in the same person across time
permit estimation of both within and between person
variability
- Within and between person variability treated as a random effect
and other variables such as age, gender .residence, season
treated as fixed effects
• TCP had a low percentage below limits of detection
• Measurements below limit of detection (LOD) were
treated as being left censored in statistical analyses
Predictive Value Positive for Identifying Persons in
the Upper 10% of the Population
The predictive value positive is the percent of the population assigned to a group that are
correctly classified.
Based upon large
within person
variances it will
require a large
number of
samples of
urinary
metabolites to
correctly identify
persons in a
population who
are more highly
exposed to CP
and CPM.
-------
CMC Biomarker Faustman
Sources of Uncertainty
Stochasticity
- Characterization of Within and Between Person
Variability
Parameter Uncertainty
- Year-to-Year Variability
- Observations below Limits of Detection (LOD)
Model Uncertainty
- Crop vs. Agricultural Job Task
- Identification of Highly Exposed Individuals
Biomarkers for Monitoring Exposure and
Effect in Populations
Physiologic Based Toxicokinetic
Models of CP Metabolism
Methodology Underlying
Integrated Framework Tool
Bayesian Based Mixed Effects Model
- Correlational structure of a multivariate
distribution used to estimate correlations
between pesticide concentrations,
metabolites, gene expression levels, and
other variables
- Markov chain Monte Carlo methods used for
parameter estimation
-------
OP Pesticide Exposures
and Neurodevelopment in
Children from Farmworker Families
KimHarley,PhD
UC Berkeley
Center for Children's Environmental Health Research
Objectives
To estimate sources, pathways and levels of in utero and
postnatal pesticide exposures of children living in an
agricultural community.
To determine the relationship of pesticide exposure and:
neurodevelopment
growth
• respiratory disease
WINTER fQ* TMI HIALTH ASSCSlMtMT Oi
MOTHER* AND CHILDREN OF SALINAS
Characteristics of
CHAMACOS Mothers (N=601)
92% Spanish-speaking
85% born in Mexico; 54% < 5 years in U.S.
96% living within 200% of poverty
44% 6th grade education or less
44% worked in agriculture during pregnancy
84% other agricultural workers in home
-------
CHAMACOS is a longitudinal birth cohort study
CHAMACOS Biological Specimen Collection
2Y 3>/,Y 5Y 7Y
Delivery 6 M 1Y 2Y 3>/,Y 5Y
•/ •/ •/
Paternal Urine
1 Maternal Blood
OP Pesticide
Oxvdemeton-methvl
Methidathion
Chlorpyrifos
Organophosphate Pesticide Use
in the Salinas Valley, 2001
Pounds Excreted in urine as
57,859 Dimethyl (DM)
34,224 phosphates
17,045 -220,000 Ibs. (42%)
Diethyl (DE) phosphate
54>945 -199,000 Ibs. (38%)
10,216
71,725 Other
32,669 -104,000 Ibs. (20%)
-520,000
-------
-------
Mary Wolff, Stephanie Engel, Gertrud Berkowitz
Mount Sinai School of Medicine
Virginia Rauh, Robin Wyatt, Frederica Perera
Columbia University
Brenda Eskenazi, Kim Harley, Asa Bradman, Amy Marks
University of California, Berkeley
Biomarkers of Prenatal OP
Pesticide Exposures
Berkeley
Mt. Sinai
Columbia
In Urine
Dialkyl
Phosphates
(DAPs)
In Blood
Chlorpyrifos
(CPF)
Early Childhood
Neurodevelopmental Outcomes
Brazelton Bayley WPPSI
Neonatal 6M 1Y 2Y 3Y 3.5Y 5Y
Berkeley X
Mt. Sinai X
XXX
XXX
Verbal IQ assessed with
-------
Early Childhood
Neurobehavioral Outcomes
Child Behavior
Checklist (CBCL)
2Y 3Y 3.5Y
Berkeley
Mt. Sinai
Columbia
Demographics of
Study Populations
Race/Ethnicity
Non-Hispanic White
African-American
Hispanic
Other
< High school
Berkeley Mt. Sinai Columbia
Mexican 97 Mex, PR 51 Domi
21
Associations with
7 Brazelton Clusters
Berkeley 6/7 No associations
Mt Sinai 6/7 No associations
EXCEPT.
-------
Prenatal OPs and Bayley
Psychomotor Development Index
Prenatal OPs and Bayley
Mental Development Index
Berkeley Mt. Sinai Columbia
(Log10DAPs) (Log10DAPs) (High v. Low CPF)
6 Months -0.7
1 Year -0.6
2 Years -1.3
6 Months
lYear
Prenatal OPs and
Child Behavior Checklist
Berkeley Columbia
2Y 3.5Y 3Y
Adj OR Adj OR Adj OR
Attention Problems 0.8 in prep
Attention Deficit/Hyperactivity 1.3
Pervasive Developmental Disorder 2.3**
In summary.
Three scientifically-rigorous, cohort studies
— Different populations
Different exposure levels and sources
Exposure measured using biomarkers in urine (metabolites)
and blood (parent compound)
Despite these differences, some patterns emerge.
In summary
Investigators
Prenatal OP exposure associated with:
Increased odds of abnormal reflexes in neonates
Poorer mental development in 2 and 3 year olds
- Poorer verbal IQ in 3'/2 and 5 year olds
- Increased odds of pervasive developmental
disorder
Martha Harnly, DHS
Intervention and Community Outreach
• Abbey Alkon, UCSF
• Michael Lipsett, DHS
Janet Macher. DHS
-------
1998 CENTERS FOR EXCELLENCE
CHILDREN'S ENVIRONMENTAL
HEALTH
With additional funding from:
California Wellness Foundation
-------
Cholinesterase Monitoring in
Washington State
John Furman
Washington State Department of
Labor & Industries
What Is Cholinesterase (ChE)?
• Enzyme
• Present in nerves, brain, and muscle
• Nervous system's "off" switch
• If 4 ChE -> ttt acetylcholine -> overstimulation
& exhaustion of
nervous system
Thank you to Jonathan H. Siekmann, Ph.D
Cholinesterase-inhibiting
Pesticides
Organophosphates
N-methyl-carbamates
Toxicity class I & II products
• "DANGER" or "WARNING" on the label
Class I LD 50 of < 50 mg oral or 100 dermal
Class II LDSOof >50 <500 oral or <1000 dermal
Pesticide-Related Illness
-tiredness, weakness, dizziness, nausea,
blurred vision
Moderate
- headache, stomach cramps, sweating,
drooling, vomiting, tearing, twitching
Severe
- urinating, diarrhea, muscle twitching,
staggering gait, pinpoint pupils, seizures,
hypotension, slow heartbeat, breathing
difficulty, coma , death
Blood Cholinesterase:
Convenient Biomarker
Red Blood Cell (RBC) ChE
- Sensitive to Organophosphates
- Measures longer-term exposures
- Slow recovery
Serum ChE
- Sensitive to most ChE inhibiting pesticides
- Measures recent exposures
- Rapid recovery
Considerations
Normal individual ChE levels vary
- Establish exposure-free baseline
- Compare periodic samples to baseline
Different analytical methods exist
- Use same laboratory
- Use same method
"Depression" is a decrease in ChE activity in
periodic sample vs. baseline
-------
Why Monitor Cholinesterase?
Detect overexposure to pesticides
Increase hazard awareness
Identify unsafe environments & fix problems
Reduce risk of possible long-term adverse
health effects
Decrease take-home exposures
ChE Monitoring in Washington:
History and Legal Authority
• 1993 - ChE monitoring recommended
• 2002-Riosv Washington
• 2003-WAC 296-307-148 adopted
• 2004 - 1st year of operation
• 2006 - Final SAC report
• 2007 - Move to commercial laboratory
Who is Tested in Washington?
Agricultural handlers of Class I and II
• Organophosphates
N-methyl Carbamates
Exposure threshold:
2004 >50 hours handling in 30 days
2005 >30 hours handling in 30 days
Pesticide Handling
Agriculture pesticide handling*
- Mixing, loading transferring applying
- Disposing of pesticides or pesticide
containers
- Handling open containers of pesticides
-Acting as a flagger
- Cleaning, maintaining equipment that may
contain pesticide residue
-Assisting with application
* See WPS for complete definition
Handler Participation
May decline participation
Employer provided training
Informed consent process with medical
provider
Signed declination statement
Averaged -12% annual declination rate
Required Actions
• Work practice investigation
- >20% depression in either RBC or serum ChE
• Exposure removal
->30% depression in RBC ChE*
or
- >40% depression in serum ChE*
*Can return to handling when within 20% of baseline
-------
Experience
# Employers
# Baseline tests
# Periodic tests
# Employees with
periodic tests
2004 2005 2006 2007*
370 312 244 219
2630 2239 1889 1859
1048 994 692 494
580 612 471 362
* Preliminary numbers
Work Site Violations
Respiratory Protection
Personal Protective Equipment
Personal clothing as exposure source
Decontamination
Pesticide Handler Training
Experience
Work practice
investigations
2004 2005 2006 2007*
(17%) (8%) (11%) (13%)
# Medical removals
(4%) (2%) (1%) (4%)
119 59 57 62
(21%) (10%) (12%) (17%)
Effects
Increased knowledge
Increased hazard awareness
Training integration
Changes in pest management practices
Improved medical services
Increased stakeholder collaboration
-------
Biomarkers of Pesticide Exposure: Lessons
for Children in Agricultural Communities
Biomarkers for Monitoring Exposure and
Effect in Populations
Elaine M. Faustman
Bill Griffith
Examples of Chemicals Applied to
Washington State Crops, 2001
Chemical class
Organophosphates
N-Me Carbamates
Dithiocarbamate
crop
Apples
Potatoes
Apples
Potatoes
Apples
Potatoes
Chemical
Azinphos-methyl
Chlorpyrifos
Phosmet
Ethoprop
Metamidophos
carbaryl
Aldicarb
Mancozeb
Mancozeb
Pounds applied
241,000
234,000
138,000
119,000
143,000
202,000
153,000
82,000
343,000
Source: "Agricultural Chemical Usage (PCU-BB)" National Agricultural Statistics Serv
Agricultural Statistics Board, U.S. Department of Agriculture
(http://jan.mannlib.cornell.edu/reports/nassr/other/pcubbAccessed05/03)
Agricultural Pesticides: Contributions of
Occupational Factors to Home Contamination
Metabolic Scheme for CP
Faustman et al. (2006)
Metabolites of Organophosphate
Pesticides
• Biomarkers of exposure
• Nonspecific Diakyl Phosphate
(DAP) metabolites
- Six DAP Metabolites
- Each metabolite can be
produced by multiple OPs
- Divided into two groups
• Dimethyl metabolites
- DMP, DMTP, DMDTP
• Diethyl metabolites
- DEP, DETP, DEDTP
• Specific metabolites
- Chlorpyrifos metabolites
• TCP, DEP, DETP
- Chlorpyrifos-methyl metabolites
• TCP, DMP, DMTP
-------
Metabolites of Organophosphate
Pesticides
Selected OPs and DAP metabolites
Diethyl OPs
chlorpyrifos
diazinon
disulfbton
ethion
parathion
Dimethyl OPs
azinophos methyl
chlorpyrifos methyl
dichlorvos(DDVP)
methyl parathion
naled
phosmet
trichlorfbn
DEDTP
DEDTP
DMDTP
DMDTP
DMDTP
DEP
DEP
DEP
DEP
DEP
DMP
DMP
DMP
DMP
DMP
DMP
DMP
DMP
DETP
DETP
DETP
DETP
DETP
DMTP
DMTP
DMTP
DMTP
DMTP
NHANES Data for DMTP in Urine
Random sample of US Population
Comparison across ages Comparison for children
in 2000-2001 (6'11 Vears old) across
time
What do these values mean for my
Children?
Samples Collected in Studies of
Farmworker Families
Types of samples collected from individuals and
their children in 3 seasons
- Urine analyzed for metabolites of OPs—collected 3
times in 1 week
- Blood analyzed for parent OPs, metabolites of OPs,
AChE in RBCs and plasma, genotypes and
phenotypes of metabolizing enzymes—collected once
- Buccal Cells analyzed for gene expression—collected
2 times in 1 week
Dust is collected from homes and autos in
thinning and non-spray seasons season and
analyzed for parent OPs
Many Values Are Below
Limits of Detection
Baseline Year
Child DETP
Quantiles of a log normal distribution
NH/
C
Fs
Q)
•j=i
Q) <»'
Q)
Q_ o
C 03
O
1,
£ 8.
kNES Compared to Farmwo
Data for DMTP in Urin
smparison to Adult Comparison to Childr
rmworkers of Farmworkers (2-5
years old)
Sl^Y^f
ll
5 50 50 0
V
5000
O'l
E'
8'
111:!,,,,,
ill I I
5 50 50 0 500 0
concentration ug/l
rker Family
e
en
Data for
farmworkers and
their children
was collected in
two different
years
12
-------
DMP in Adult Urine: QQ Plots to
Estimate Population Distribution
Group of 8 Higher
Exposed
Individuals
Detection
Limit
•:•..',.-;•.'- ; ol'Sr.:; i'l • : :-i :,=;i :_•..-. ;,i
Distribution of Adult DMTP Metabolite
Concentrations
1 oono.n.,40. in.,™,,
Concentration (ug/L)
1000
15
Distribution of Child Urinary DMTP
Metabolite Concentrations
ChiMren
Distribution of Adult DMTP from year 1:
Impact of Crop
Baseline Year
Distribution of Child DMTP from year 1 to year 4
of CMC study: Impacts of year to year variability
Child DMTP
-------
Assessing Children's Pesticide Exposure
via the Take-home Pathway
Adult M ^^^> Child
exposur^^^^ ~^^^ exposure
Car dust
Assessing Children's Pesticide Exposure
via the Take-home Pathway
ojtola
xposur^A j^> expos
%k^^^ ^^^-^
Car dust
i\ S\
Adult
urine
Child
urine
Azinphos-methyl Take-home Pathway
Child
urine
Adult
urine
The dashed black lines that connect the samples illustrate the correlations between the sample
concentrations. The lines are weighted according to the strengths of the correlations. The correlation
statistically significant if the 95% posterior probability intervals (in parentheses) do not include zero.
Urinary
metabolites
higher
in adults who
worked in pome fruit and their children
Adult DMTP in Urine
8
§
1
|8
O
O
Non-Pome .
Fruit )
/ J
//
1 10
.
• '/ '
/
Pome
Fruit
P<0.001
Child DMTP in Urine
8
T~
§
§
o
o
Non-P
Fruit
/
7
100 1000 1
Urinary DMTP ug / liter
Coronado etc
/» •
//
• '/ Pome
' / Fruit
P=0.003
10 100 1000
I., Env. Hlth. Persp., 2004, ?006
Two longitudinal studies of OP metabolites
used to estimate within and between variability
• Multiple measurements in the same person across time
permit estimation of both within and between person
variability
- Within and between person variability treated as a random effect
and other variables such as age, gender .residence, season
treated as fixed effects
• TCP had a low percentage below limits of detection
• Measurements below limit of detection (LOD) were
treated as being left censored in statistical analyses
Within and Between Person Distributions for TCP
• Population based
collected at 3
times separated
by 2 days
•90 Children 3-14
yrs old and 263
samples
• Only 20 samples,
8%, below limit of
detection
• Covariates of
gender, age,
residence were
treated as fixed
effects
• NHEXAS data
Shared by John
Quack enboss
NHEXASdata base
Within Child
Geometric standard deviation 2.0 .N Distribution
Urinary TCP (micro-moles/liteo
-------
Within and Between Person Distributions for TCP
NHEXAS database
Maryland: TCP
Geometric standard deviation= 1.5
• Population
based random
sample collected
over 1 year
• Up to 6
samples per
person, samples
separated by 2
months
• 79 individuals
and 341
samples
•Only 14
samples, 4%,
below limit of
detection
• Covariates of
gender, age,
season were
treated as fixed
Geometric standard deviation= 1.8
Between Person
Distribution
90th
Percentile
Within Person
Distribution
Predictive Value Positive for Identifying Persons in
the Upper 10% of the Population
777© predictive value positivt
correctly classified.
:s the percent of the population assigned to a group that a
Based upon large
within person
variances it will
require a large
number of
samples of
urinary
metabolites to
correctly identify
persons in a
population who
are more highly
exposed to CP
and CPM.
Urinary TCP (micro-moles/liteo
Number of Mes
Sources of Uncertainty
Stochasticity
- Characterization of Within and Between Person
Variability
Parameter Uncertainty
- Year-to-Year Variability
- Observations below Limits of Detection (LOD)
Model Uncertainty
- Crop vs. Agricultural Job Task
- Identification of Highly Exposed Individuals
Physiologic Based Toxicokinetic
Models of CP Metabolism
Integrated Framework Tool
Diaphragm
Thinning
Diaphragm
Non-spray
-------
Methodology Underlying
Integrated Framework Tool
Bayesian Based Mixed Effects Model
-Correlational structure of a multivariate
distribution used to estimate correlations
between pesticide concentrations,
metabolites, gene expression levels, and
other variables
- Markov chain Monte Carlo methods used for
parameter estimation
Hypotheses to be Tested
. Knowing the genotype/phenotype for key genes that metabolize
CP (biomarkers of susceptibility) will improve prediction of
- Exposure response
- At risk individuals in agricultural communities
. Knowing polymporphisms of oxidant responsive pathways will
allow us to:
- Better evaluate the potential for genomic biomarkers of early
response with OP metabolites of exposure.
- Better predict relationship of biomarkers of effect (AChE) to
respond in dose-response manner to the OP exposures in
adults and children.
- Better predict whether "omic" biomarkers of disease are
correlated with OP exposure.
GO-Quant based
quantitative pathway analysis
NIEHS/EPA Center for
Child Environmental Health Risks Research
University of Washington
\
Using Markov Chain Monte Carlo
Methods to Estimate Correlation Structure
Metabolites
above LOD
Replace missing
values by LOD
Univariate Data
Simulation
Multivariate Data
Simulation
-------
Phthalates Exposure in Childhood:
Is there Evidence of Harm?
Maida P. Galvez, MD, MPH
Region II PEHSU Director
Phthalates
Concerns exist about the potential for
phthalates to act as endocrine disrupters,
largely based on animal studies and a
small but growing body of evidence in
human studies.
Hormonal effects of phthalates
Animal Studies
DEHP fgestational age
DBP I gestational age
BBP fbody weight at lactation
DBP, | serum testosterone
DEHP
BBP I Anogenital distance in male infants
MBP Decreases testicular function
Human Studies
V
V
V
V
Phthalates Legislation
Several countries around the world,
beginning with the European Union, have
subsequently banned phthalates in
children's products.
Phthalates in the Media
Widespread media reports on the potential
harms of fo-x-Sc toys and other children's
products containing phthalates have
raised parental anxiety about the impact of
environmental exposures on their children.
-------
Primary care pediatricians
What Parents Ask
Faced with clinical questions that are
difficult to answer:
- limited medical school training in children's
environmental health
- Especially limited knowledge of emerging
exposures of concern such as phthalates
-Conflicting messages in the media
Where are phthalates found?
Is this pacifier harmful to my child?
How do I know if toys contain phthalates?
Why was it banned?
What health effects should I look for?
Should I avoid phthalates if I am pregnant?
What substitutes can I use for my child?
Goals for this Session
To describe:
• exposure levels in pregnant women,
toddlers, and school aged children
• sources of exposure
• known and potential health outcomes
Is there Evidence of Harm?
Pregnant women in New York City
Dr. Robin Whyatt
Columbia University Center for Children's Environmental Health
6-24 month old infants from California, Minnesota, and Missouri
Dr. Sheela Sathyanarayana
University of Washington, Seattle, Northwest PEHSU
Pregnant women and 4-8 year old children in New York City
Dr. Mary Wolff
Mount Sinai Center for Children's Environmental Health
Phthalates Exposures are Widespread
MEP MBuPhth MbZPhth MECPP
NYC Pregnant Women (n=246) 232 37.5
NYC Pregnant women (n=382) 380
CA, MI,M02-24mos(n=163) 65
NYC 6-8 yo girls (n=30) 100
NYC 6-8 yo boys (n=101) 152
NYC kids (n=35) 159 samples 166
37.5
36
19
50
68
56
17.5
22
15
22
48
38
-
35
4
111
123
139
-------
Summary of Findings
Sources are varied
- Products used
- Indoor air
Good biomarkers
Health outcomes
-Gestational Age
-Anogenital Distance
-BMI
-Asthma
What's the evidence for Phthalates in Cosmetics?
• EWG report on phthalates in cosmetics
• Skin Deep Database
• Safe Cosmetics Fact Sheet
• 12 Ugly Truths Behind the Myth of Cosmetic Safety
Campaign for Safe Cosmetics
How fJm •* ymr bejuty producb*
Thi
Skin Dgep r»
Click h«rt to find Outt
Pocket Guide to Plastics for
easy reference
Front of card Back of card
&
&
| Mount Sinai Community
rteahh Bulletin
Quit* Guds to Sate Plasl
E5
Key areas for discussion include:
• What is the current evidence for adverse health
outcomes?
• What are the research gaps?
What health messages on phthalates can we
share with families now?
What policy issues remain unresolved?
Acknowledgements
Barbara Brenner, DrPH (PI)
Julie Britton, PhD (Co-Pi)
EunpaChae, MPH
LuzClaudio, PhD
Joel Forman, MD
MaidaGalvez.MD (Co-Pi)
Jim Godbold, PhD
Jessica Guttierez
Philip Landrigan, MD
Laura Liao, MS
Ana Mejia
Kim Morland, PhD
Arkeyris Richiez
Susan Teitelbaum, PhD
Nita Vangeepuram, MD
Sarah Williams
Mary Wolff, PhD (PI)
1
Acknowledgements
The Growing Up Healthy CAB:
- Children's Aid Society
- East Harlem Pediatric/Child Health Subcommittee
- Little Sisters of the Assumption
- Mount Sinai Pediatrics Associates
- Mount Sinai School Based Health
- NYCDOHMH's East Harlem District Public Health Office
- North General Hospital
- Settlement Health
Susan Resnick at the NYCDOHMH
Jodi Siskind, Jessica Kobil and Cherita Raines
-------
Acknowledgements
NIEHS/EPA Children's Environmental Health Research Center
NIEHS/NCI Breast Cancer and the Environment Research Center
(Fox Chase/MSSM)
- NIEHS Grant #2 P01 ES009584
- NIEHS and NCI Grant SES0102771
Environmental Protection Agency
- EPA Grant SR827039
- EPAGrant#RD831711
Mount Sinai Pediatric Environmental Health Specialty Unit
Agency for Toxic Substances Disease Registry
- ATU Grant #300014
General Clinical Research Center
- NCRR Grant SM01-RR-00071
-------
Case Study on Phthalates
Case Study on Phthalates
Diiunci PND-2 |m
I
• Control
OEHP
Mil* Female
Case Study on Phthalates
Case Study on Phthalates
Exposure
Assessment
Biomarkers of Exposure
Effect/Susceptibility
Outcome
Phthalate diesters Phthalate monoesters
Case Study on Phthalates
Case Study on Phthalates
48 hour personal air 3" mester 2 week integrated indoor air 32™ week - delivei
-------
Case Study on Phthalates
Phthalate Diesters In Air Monoester Metabolites In Urine
Case Study on Phthalates
Steroid synthesis and
metabolism
DEHP
Xenobiotic metabolism
Oxidative stress
Fatty acid transport
Tropho blast
differentiation
Case Study on Phthalates
Case Study on Phthalates
Aim 1: Characterize phthalate exposures
during pregnancy among NYC African
American and Dominican women.
Case Study on Phthalates
Case Study on Phthalates
-------
Case Study on Phthalates
Case Study on Phthalates
MCPP
MEP
MBZP
£ MiBP
E
MnBP
-MECPP
§ MEHP
MEOHP
MEHHP
Aim 2: Examine effects of prenatal phthalate
exposures on modulation of gene expression
in placental tissue.
] 1000 1500
Geometric Mean (95% Upper Confiden
Case Study on Phthalates
Case Study on Phthalates
Aim 3: Examine effects of prenatal phthalate
exposure on gestational age and fetal growth.
Case Study on Phthalates
Case Study on Phthalates
-------
Cohort: 163 Infants
Sex Race
Geographic
Ages (mo)
Socio-Economic Status
Distribution of Phthalates (mcg/L)
Number of Phthalale Metabolites Found in Infant Urine Samples (N=163)
SO
Number of Urine Phthalate Metabolites
Product Type Mean Z-s
N % Subgroup N % Subgroup N %
<= 8 months 42 (26) > 8 months 112 (74) All Infants 154 (100)
Significant
-------
i:
-------
Results of Regression Analysis
Significant (p-value)
MBP (0.048)
MEP (0.005)
DEHP metabolites
MEHP(O.OI7)
MEOHP(O.OOI)
MEHHP (0.002)
MMP (0.053)
MiBP (0.097)
Not Significant
MBzP (0.826)
MCPP(0.59I)
* Mixed model including 106 boys and 165 visits
Clinical Implications
In Rodents
- At birth: Shorter AGO, impaired testicular descent,
hypos padias
i Later Low sperm count, rarely testicular tumors
Our Study of Humans Suggests
• At birth: Shorter AGO (some, but most NS, decrease in
testicular descent, smaller penile volume)
Future studies needed to determine
clinical correlates in humans
Acknowledgements
U Rochester
Shanna Swan
Fan Liu
U Washington
Catherine Karr
Paula Lozano
UMO
Robin Kruse,
Sara Stewart, Lynn Teague
UCLA
Christina Wang, Cathy Mao
Dana Barr.Antonia Calafat
Jim Overstreet, Charlene Brazil
U Copenhagen
Katharina Main
Bruce Redmon, Chris Ternand
-------
THE MOUNT SIN
"AL. HEALTH &
•ijfr
Urinary phthalate metabolites in 3 populations
MEP, adjusted GM ug/gC
MCPP, adjusted GM ug/gC
*BPA: - with use of drink containers (p= **, wrong direction)
*BPA: no correlation with "foods that come in cans"
*BP3: +• with use of sunscreen (p<.001)
Phytoestrogens: 0.17 (Dai) 0.33 (Gen)
Phenols: 0.35 (BPA)
-------
EHigh-molecular weight
ELow-molecular weight
ZHigh-molecular weight
ZLow-molecular weight
26.0
25.0
22.0
21.0
26.0
25.0
Quartilas of low-MWP
Maternal pre- pregnancy BMI (kg/m2)
predicted from phthalate and
creatinine biomarkers Children's
Environmental Health Study, 1998-
2002.
Adjusted for race, infant sex, gestational age, In-creatinine; restricted to samples with
creatinine >20 mg/dL. Rs with creat = .49 (Hi) .42 (DEHP .39 (Lo)
23.0
22.0
21.0
Quartiles ofhiah-MWP
tmpbmiph.xls
-------
-------
Improving Asthma Outcomes:
2007 NAEPP Guidelines focus attention on
education and environmental interventions
David Rowson, Director
Center for Asthma and Schools
US EPA Indoor Environments Division
Overview
Overview of the 2007 NAEPP Guidelines for the
Diagnosis and Management of Asthma
Highlight Guidelines recommendations for patient
education and control of environmental factors
Introduce EPA Initiative to accelerate adoption of
best practices
National Guidelines for the Diagnosis and
Management of Asthma
National Guidelines for the Diagnosis and
Management of Asthma
New focus on monitoring asthma control as the goal for asthma
therapy and distinguishing between classifying asthma severity and
monitoring asthma control.
New focus on impairment and risk as the two key domains of
severity and control, and multiple measures for assessment.
• Modifications in the stepwise approach to Managing Asthma Long
Term.
New emphasis on multifaceted approaches to patient education and
control of environmental factors and comorbid conditions that affect
asthma.
• Modifications to treatment strategies for managing asthma
exacerbations.
Guidelines Frame-work: 4 Essential Components
of Asthma Care
Assess and Monitor Asthma Severity and
Control
Education for a Partnership in Asthma Care
Control of Environmental Factors and Comorbid
Conditions
Medications
Educating patients, families, and providers
Education for a Partnership in Asthma Care:
Self-management education is essential, should be integrated into
all aspects of asthma care, and requires repetition and
reinforcement.
Patient education
a Many potential sites/points of care outside office setting
a Written asthma action plan emphasizes both daily management
and worsening asthma
a Attention to cultural, ethnic factors and health literacy
Provider education
a systems-based interventions and
a effective clinician education programs
-------
Multi-faceted approach to control environmental
factors
Multi-faceted approach to control environmental
factors
Reducing exposures to inhalant indoor allergens and irritants improves
asthma control
a Determine exposures and sensitivities—use skin testing or in vitro testing for
persistent asthma
a Consider allergen immunotherapy for persistent asthma and clear, consistent
exposure/response
Multi-faceted approach is most effective
a Tobacco Smoke
a Dust Mites
a Animal Dander
a Cockroach
a Indoor Mold
a Pollen and Outdoor Mold
a Smoke, Strong Odors,
Sprays, Formaldehyde,
VOCs
a Vacuum Cleaning
a Exercise or Sports
Asthma in the US
20 M, including 6.3M kids
a 2M ER visits
a 14M missed school days
Some National indicators leveling off, but at all-time highs
a Prevalence, ER visits, hospitalizations
Important disparities in morbidity and mortality continue
a Children and the elderly
a African Americans, Native Americans, Hispanics
$16.1 B in annual costs
a direct health care costs, e.g. physician services-$11.6 B
a indirect costs, e.g. school/work absence, mortality -$4.5 B
H
ealthy People 2010: How are we doing?
Healthy People 2010
Objective
on'hoTto^th'em^raprrly ^'^ mstmctl0n
'"™°nm"anl£a"Sa^an"mh",a
EEr"™*"™""1""
therapy
Written asthma management plan from their HC
schoTan'd work environments1 ^ ^^
Formal patient education, including information
condl3nIP3rt0fthem3n3Sement0fthe'r
2010
Target
988%
92%
87%
7,%
38%
50%
30%
Midcourse
Status
96%
=„,.
76%
"'"•
35%
4,,.
124*
Driving Improvements in Asthma Care through
Increased Patient Education/Control of Triggers
Health Care Provider outcomes
a Increasing numbers of patients receiving
written asthma management plans
education
assistance with trigger avoidance
Patients/Caregivers
a -30% taking essential environmental control actions
• Health Plan Results
a Widespread promotion of guidelines to providers
a Increased support for education/environmental interventions
a Business case is becoming more evident
Accelerating progress through Community-based
asthma care
Asthma Health Outcomes Project
a Identified program elements linked to health
outcomes
Change Package of Successful Strategies
a Compendium of field tested actions
Network of programs driving toward best
practices and outcomes
a www.asthmacommunitynetwork.org
-------
Cambridge Health Alliance
High-Performing
Collaborations & Partnerships
• School System
• Department of Public Health
• Advocacy with city government
and politicians
Integrated Health
Care Services
• Registry as a "connector"
• EMR supporting "best pra
• Performance outcomes linked to
• Educated clinical care teams
on evidence-based guidelines (NHLBI)
Strong Community Ties
• Linkages with School Nurses
• Chief of Pediatrics is co-chair of
Healthy Children's Taskforce,
Cambridge, MA
Tailored Environmental
Interventions
•Asthma Action Plan for each child
• Referral to Healthy Homes Program
(RN home assessment, patient
education, and home supplies
Committed Program Champions
• Providers, nurses, and staff at practice site:
• CEO and Senior Leaders
• Chief of Pediatrics and Family Medicine
•Ambulatory Administration
• Performance Improvement Department
• IT Department
Communities in Action Network
Objective
Reduce ED Visits
Reduce Hospitalizations
Increase Symptom-Free Days
Patients receiving Education
Patients receiving Assistance to
Assess/Reduce Triggers
HP 2010 Target
30% - 50%
(15-80 per 10,000)
38% - 45%
(8-25 per 1 0,000)
>10 per 14 days
30%
50%
Best in Class
Results
50% - 75%
50% - 80%
10.4 days in a row
100%
100%
Communities in Action Network
Mobilizing 1000 Communities to deliver quality
asthma care
Looking Ahead
Educate clinicians and others in health care community
to follow new NAEPP Guidelines
Clinicians collaborate with community resources to
deliver comprehensive care addressing all 4 components
of asthma care
Your programs are leaders in understanding effective
care
Join the Communities in Action Network
www.asthmacommunitynetwork.org
Join us May 1-2 at the 3rd National Asthma Forum
www.epaasthmaforum.com
-------
Prenatal and early postnatal
exposures and asthma risk-
How???
Rachel L. Miller M.D., FAAAAI
Columbia Center for Children's Environmental Health
(CCCEH)
Columbia University
sntal Health Workshop: Discover, Treat, I
Asthma is a complex disease
Mediated by
-genetic predisposition
-environmental exposures
- host factors eg obesity, psychosocial
- infections
Epidemiological support:
Prenatal exposure to ETS
ETS is associated with
- impaired respiratory function
-transient wheeze,asthma, and/or
respiratory infections in infants, young
children, and adolescents
Additional prenatal exposures
Increase asthma risk?
- Low maternal intake of vitamin E, zinc
-Use of antibiotics
- Respiratory infections during pregnancy
-Ambient air pollution eg PAHs
Decrease asthma risk?
- Probiotics
- Multiple pregnancies
•pidemiology 2006;17:138-144
-------
Epidemiological support.
Early postnatal exposures
Dust mite allergen during infancy
- determinant for later childhood asthma
Dog, cat allergen
- associated with protection from later childhood
wheeze
Combustion-related pollutants
- associated with later childhood sensitization to
dust mite
- reduction in FEV.,
Prenatal PAH, postnatal ETS and
respiratory score (CCCEH)
Analysis for Main Effects
Analysis for Interactions
12 months
(n=263)
Intercept 0.68
Sporik R et. al. NEngl J/Wed1990;323:502-507
Remes et. al. J of Allergy and Clinical Immu,
Ponsonbvet. al. Clin Exo Allerav 2001:31:1!
-------
Epigenetic-mediated mechanisms
Heritable changes* in gene expression
that occur in the absence of alterations
in DMA sequences
' at least between cells
Epigenetic regulation
DMA methylation
- covalent addition of a methyl group to cytosines in CpG
dinucleotides
Chromatin packaging of DMA via post-translational
modifications of histones
- egs. acetylation,methylation,phosphorylation
Believed to occur predominantly prenatally and
shortly after birth
May influence gene expression differentially
throughout lifespan
Eg: T helper cell differentiation
Proallergic IL-4 production and Th2 differentiation
- demethylation of sites at the prox promoter and
conserved intronic regulatory element (CIRE) in 1st
intron of the IL-4 gene
- hypermethylation of sites in the counterregulatory IFNy
promoter
Th1 differentiation
- methylation of a highly conserved DNasel-
hypersensitive region at the 3' end of the IL-4 locus
-------
In vivo study of methylation of IL4 gene
in asthma-like mouse models
AspAg Dl
Collect CD4+ cells
Isolate genomlc DMA
Bisulfite conversion
PCR amplification
Pyrosequence of IL4, IFNy gene:
Quantify methylation level
Methylation profiling using methylation
sensitive restriction fingerprinting
• Study population/samples: CCCEH cord
blood
PAH exposure
- high prenatal PAH exposure: highest
quartile prenatal air PAHs/high PAH-DNA
adducts
- low exposure: lowest quartile PAHs/low
PAH-DNA adducts
-------
Conclusion
Acknowledgements
Prenatal and early postnatal exposures impact risk
for later asthma
Both immune-mediated and epigenetically-
regulated mechanisms likely contribute
Much more cohort-driven mechanistic research
needed to assess:
- dose of specific exposures
- time periods of increased susceptibility
- interactions btw genetics and epigenetics
Frederica Pererc
Graham Barr
Chris Espino
Ginger Chew
Inge Goldstein
Alina Johnson
Manisha Ballane
Andria Reyes
Umaima Al-alem
Cynthia Lendor
Kathleen Moors
Rachel Miller
Rafael Narvaez
Matt Perzanowski
University of Cincinnati: S. M. Ho, V\
CDC: D. Barr, T. Bernert, E. Gunter,
Schleicher, L. Needham, D. Pascal,
Jullie Herbstrr
Susan Edwe
Jmming Liu
Deliang Tang
Funding
The CCCEH research has been made possible by funding
from:
..._S01549
IS00260
'50ES01590
i Star grants: R-82860901; R-827027; RD-83209601
RD-832141:RD-83209601
-------
The Center for Childhood Asthma in the
Urban Environment
Elizabeth Matsui, MD MHS
Patrick Breysse, PhD, Director
Gregory Diette, MD MHS, Deputy Director
Johns Hopkins University
Bedroom Cockroach
Allergen
m
TJ
10
8
6
4
2
0
Median
P>0.05
Asthma Control
Diette G etal, Env Health Perspective, In Press
3500 n
3000
2500-
2000-
1500-
1000
500
0
Bedroom Settled Dust
Allergen
A11P>0.05
Dust Dog Cat Mouse
Mite
Diette G etal, Env Health Perspective, In Press
Recent Asthma Symptoms
Medication use
3 -,
_2
1
0
*adjus
exposu
Matsui E eta
& Rescue
}J
III
I '
I
ted for age, sex, atopy, cockroach sensitization and
re, public health insurance, and study visit
, Ann Allergy Asthma Immunol. 2006 Oct;97(4):51 4-20.
Asthma-related Health Care Use
OR(9S%CI)
1
• Hospitalization
Adjusted OR:
69.9 (5.8-838.9)
• 9/10
hospitalizations
occurred among
sensitized/high
exposure group
UD Visit ED Visit
djusted for age, sex, atopy, cockroach sensitization and exposure,
blic health insurance, and study visit
Bedroom Air Pollutants
Diette G etal, Env Health Perspective, In Press
PM2.5 PM10 N02 Ozone
-------
Distribution of Indoor PM in Children's Bedrooms
Figure 2. Distribution of Indoor and Ambient Fine and Coarse PM
Boxplots display indoor and ambient fine and coarse PM. Indoor PM concentrations were significantly higher than
ambient. The red dashed line demonstrates the EPA annual limit for ambient PM25 Over 75% of homes had indoor PM
concentrations that exceeded this limit.
p<0.01
Indoor Coarse Ambient Coarse
Extreme outliers not shown
Acknowledgements
Funding
- EPA
- NIEHS
Investigators
- Peyton Eggleston
- Patrick Breysse
- Gregory Diette
- Nadia Hansel
- Elizabeth Matsui
- Francesca Dominici
- Timothy Buckley
Staff
- Study Staff
- Laboratory Staff
- Exposure Assessment
Core
- Data Management Core
Community Advisory
Board
- Adrian Mosley (chair)
Indoor PM Exposure and Asthma Morbidity
Outcomes
Cough/wheeze/ chest
tightness
Slow/stop activities
Limited speech from
wheeze
Nocturnal Symptoms
Symptoms with
running
Beta agonist use
Coarse PM
(per 10 ug/m3)
IRR
1.06
1.13
1.14
1.10
1.03
1.10
*Adjustedfor age, gender, race, socioeconom
P-value
0.03
O.01
O.01
O.01
0.33
O.01
FinePM
(per 10 ug/m3)
IRR
1.02
1.01
1.04
1.02
1.05
1.03
P-value
0.21
0.47
0.19
0.20
O.01
0.05
c status Presented ATS 2007
-------
Clinical Experience with the
invironmental Management ol
-thma & NAEPP Expert Report 2007
James M Seltzer, MD
Clinical Professor of Medicine
University of California, Irvine
School of Medicine
Co-Director
Pediatric Environmental Health Specialty Unit,
UCI
US EPA Region IX
Three Questions
What is my experience as an
allergist/immunologist caring for children with
asthma as this disease relates to environmental
factors?
What is my experience as a PEHSU director
responding to inquiries from children with
asthma, their parents, and other involved
entities/persons regarding environmental
factors?
What is the significance of the new asthma
guidelines for the clinician in his office?
- Primary care
- Specialist
4 essential com^
asthma care
.tsof
Assessment and monitoring
Relevant or potentially relevant environmental exposures
Compliance with exposure reduction
• Response to exposure reduction
• Monitoring of future exposures
Controlling factors contributing to asthma severity
• Environmental factor exposure reduction and minimization
(or possibly, exposure enhancement) - "environmental
control measures"
• Co-morbid conditions
-
October 11, 2008
James M Seltzer, MD
-------
4 essential com^
asthma care
Jbsof
armacologic and immunologic treatment - stepped
care
Anti-inflammatory "controller" medications still the mainstay for
asthma control
Specific immunotherapy can reduce the risk of future asthma
development
4. Patient and physician education
• Asthma mechanisms, including effect of environmental
exacerbants
• Medication use
• Relevant environmental control measures
• Written action plan
October 11, 2008
James H Seltzer, HD
jals of asthma thei
ctive asthma control - define it
imal therapeutic regimen, e.g., number of
idications for asthma and other allergic
isease
Minimize need for health care professional
intervention, e.g., doctor's office, E.D., hospital
Affordable
Convenient
Practical, i.e., doable
-------
-------
Neurodevelopment, Autism, and
Mercury: Biomarkers and
Epidemiologic Approaches
University of California Davis,
M.I.N.D. Institute
Outline
Outcomes
Literature on:
— Hg & Neurodevelopment
- Hg & Autism: vaccines
- Hg & Autism: non-vaccine sources
UC Davis CCEH: The CHARGE Study
- Goals, methods & results for Blood Hg
Discussion & Next steps
Outcomes
What is Autism?
Developmental delay or deficits
Mental or Cognitive:
Pervasive developmental disorder defined as
characterized by three behavioral domains:
— Executive function
Neuromuscular
Sensory deficits
Social: autism
^Deficits in social interaction
>Communication: Language impairment/delay or
unusual speech patterns
> Repetitive behaviors and/or restricted interests
Facts about Autism
Male: female ratio is 4
1 in 150 (=60-70 per 10,000) |
> Strong genetic component 1
> 60-90% concordance: monozygotic twins
* Multifactorial
* Wide variation in severity, trajectory
Historically attributed to 'bad parenting'
, Now known to have a neurobiologic basis:
aberrant brain development
Neural Substrate of Autism
Anatomical, electrophysiologic, MRI
fMRI: esp face processing
Highly diffuse throughout the brain:
— Cerebellum
- Hippocampus
- Amygdala
— Cerebral cortex
=> early insult
Purkinje cell los
-------
Mercury and Neurodevelopment
Mercury: food contamination episodes
• 1953-1961 Minimata, Japan, chronic
• 1970'slraq
- in utero exposure ~ mental retardation, physical
impairments, seizures
- autopsies showed abnormal neuronal migration,
disorganized cerebral cortex
Mercury and Neurodevelopment
Chronic Hg intake via fish consumption - (lower levels)
* Faroe Islands (n~900) Grandjean et al 1997, Debes 2006
prenatal exposure: maternal hair, cord blood, cord tissue
Seychelles Islands Davidson et al 2005
— at 5.5 years: no deficits in language, visual-motor integration, various
cognitive domains
r Proj ect Viva (n= 13 5) Oken et al 2006
maternal hair mercury
- at 6 months : deficit in visual recognition memory
— able to separate beneficial effects of fish consumption from harmful effects
RCT of dental amalgams in school-aged: no effect
Mercury and Autism: Vaccines
Controversy: thimerasol as preservative
breaks down to ethyl Hg and thiosalicylate
Polarization "Autism: a novel form of mercury
poisoning" (Bernard et al)
Removed from most childhood vaccines in 2001/02
Numerous ecologic studies using before/after
comparisons
Few studies with individual-level data:
Verstraeten et al of CDC... Vaccine Safety Datalink
Rh" and thimerasol-containing rhogam
Clarify: issue of MMR is unrelated
Sources of Hg:
Combustion of fossil fuels
Consumption of seafood or ocean or freshwater fish
Erosion of dental amalgams
Occupational exposure from mining
Direct contact from damaged mercury thermometers,
blood pressure cuffs, barometers, incandescent lights,
or batteries.
Dermal absorption from skin-lightening cremes
Use of nasal sprays, ear wax removal products, contact
lens solutions
Vaccines
Studies of (
) Hg & Autism
nonvaccrne
Palmer et al (2006): TRS emissions inventory, Hg only & autism
rates by school district
Windham et al (2006): HAP model for multiple ambient
Both were ecological
Think about timing!!
-------
CHARGE
* ildhood utism isk from
enetics andJhe nvironment
To identify causes and contributing factors
for childhood autism:
To determine mechanisms of susceptibility
for childhood autism
Blood
Mechanisms for Xenobiotics
METHODS
Consumer products
Medical history
-------
Autism or Developmental Delay
Population-based Controls
o
t H/\ Rr, r >
~y
Confirmation of diagnosis:
Parents interviewed:
Specimens:
-------
Hair Hg measurement - time course
JCG Hair, Root(O) to Tip (43),
Cut
SrK
Ba/
Hg/
Pol
Statistical Analysis
1 .E-06
13579 1113151719212325272931333537394143
RESULTS
Log Hg and Covariates by Case Status
-------
Prediction of log(Blood Hg)'
Autism or ASD
Ate tuna (1+ servings/wk)
Ate ocean fish ( " )
Ate freshwater fish (" )
Beta P-value
-0.01 0.95
0.56 0.001
0.68 O.0001
Hg amalgams x chew/grind teeth 0.15 0.004
Nasal spray or ear wax removal 0.5° n no
* Multivariate analysis to adjust for confounding
Subjects weighted to adjust for differential pa
Discussion
Timing: Current concentrations of blood metals in
children 2-5 years of age unlikely to represent
causal factors:
possibly concommitant, or downstream of ASD,
Some authors suggested abnormal metabolism or
faulty excretion of metals in children with autism
Chelation
Statistical analyses validate use of questionnaire
data about recent exposures to predict current
blood Hg level
Future Work on Metals
Earlier time windows for causal factors:
- Analyses of baby locks (first haircuts) currently
underway
— Newborn blood spots
- Maternal hair (if long enough)
Evaluate subsets: early onset/regressive
Gene x environment interaction: GSTM1, GSTT1
Develop a pharmacokinetic model of life-course
Hg profiles (need funding!)
Analysis of other metals: Pb, Cd, As, Mn
-------
Be in CHARGE !
Grateful thanks to:
Lesley Deprey
Carrie Jones
Beth Goodlin-Jones
Susan Bacalman
Nicole Tartaglia, Steve
Nowicki, Jean Sakamura
Melissa Rose
Carola Gutierrez de King.
Susana Gonzales, Caroline
Grantz, Angelica Guzon.
Eva Long, Cynthia
Contreras, Devon Baird
Special Thanks to our Funders
CHARGE AU Pool CHARGE DD Pool CHARGE
AU (n=341) (n=
Male sex of child
Parents' Race:
White
Black
DD (n=54) (n=299) GP (n=lC
GP Pool
(n=1240)
One or Both Parents Hispanic
Non-Singletons
Primiparous
Mother's age >35 Years
(at Birth of Child)
MotherOsEduation <12yrs
Outside USA orMexicc
sntMethodforDelivery
10.3
33.8
42.8
25.5
10.3
17.3
13.0
42.6
68.5
25.9
37.1
23.6
21.1
22.8
7
-------
"Genetic and Social Modifiers in
Environmental Neuroepidemiology: The
Role of Context in Chemical Exposure"
Robert Wright MDMPH
Department of Pediatrics,
Children's Hospital, Boston,
Department of Environmental Health
HSPH
• Fitted values
Biological Vulnerability
• Construction of the central nervous system
(CMS) begins in utero,
• Continues throughout childhood and
involves the production of 100 billion nerve
cells and 1 trillion glial cells.
• Cell migrate, differentiate, and form
synapses
Synapses
Transmits signals between neurons
nEnvironmental stimuli will cause neurons to fire
nNeuronal/synaptic firing is a signaling process to
mold the synaptic architecture of the brain
How does the Brain Build this
Network?
• Some of it is stochastic
nSynapses are made by the billions, and in
some respects randomly, between neurons.
We make a net gain in synapses from fetal life
till about age 2 years
nThen the number of synapses in our brain
starts to decrease
.Why?
-------
Synaptic Networks
Environmental Stimuli cause nerves to fire:
When they fire neurotransmitters are released
into synaptic junctions
This releases growth factors- signals that this is an
important neuronal connection (i.e. it gets used)
In other words there is a "natural selection"
process
n Functional synapses release growth factors
n Nonfunctional synapses do not release the growth
factors
Hebb Synapses
So how do Environmental
Chemicals affect Development?
• At "low" doses (blood lead around 5-10 ug/dL)
n Lead will interact with Protein Kinase C
• Stimulate neurotransmitter release
• Neurons fire in the absence of an appropriate environmental
stimuli
n Lead mimics calcium
• Calcium is critical to nerve signal transmission
• Calcium enters neurons during depolarization
• Lead blocks calcium channels
Lead and the Brain
Net effect
n Lead stimulates nerves to fire in a more stochastic
fashion
n Lead also inhibits neurotransmission (both
appropriate neurotransmission and inappropriate
neurotransmission)
Changes the underlying synaptic architecture, making it
less efficient
Plasticity
The brain's capacity to diminish the effects of
toxic insults through structural/functional
changes
This occurs through the same processes as synaptic
selection
In other words plasticity allows for new connections to
be made which improve function following an insult
Maladaptive vs adaptive plasticity
Neurodevelopment and Social
Environment
1 Chronic Stress known to impair
memory and learning capacity
-------
Non-chemical Toxicants-
Psychological Stress
• Psychological stress - activates HPA axis
Increases cortisol
• Hippocampus - highest density of
glucocorticoid receptors
• modulate neuro and synaptogenesis
• acutely, stress enhances memory formation,
• chronic stress appears to inhibit it
Social Environment and Pb
• Guilarte et al
• Lead poisoned animals during lactation
• Randomized to 2 groups
nAnimals raised in social isolation
Animals raised in groups with social
stimulation
• Tested on memory in Water maze
Acquisition Time
Probe Test
A. |B.
140, . £ 45.
-120- £ JO
liu ill*
E-HiU l-Hai E-CB I-PB i ' E-H20 ' I-HSO ' E-Pb ' l-Pb
CondMon f Condlllon
Enriched neuron
impoverished rwuron
Can Reducing Stress be a
Treatment?
• Mexico City
• Coopersmith self-esteem administered to
mothers when child 24 months of age
• Cross-sectional analysis
• Covariates
Blood Pb, mom's IQ, mom's education, child's
sex,
-------
^^
Main Effect of Maternal
Self-Esteem
md!24 | Coef P> 1 t [95% CI]
Blood Pb | -.11 0.569 -.50 .276
autoes | .46 0.006 .12 .78
Adjusted for Maternal IQ, education, Infant Sex,
g-
JR.
1
g.
i=.
!
1°'
"*'V*V- '-v Blood Pb and MDI
»Jfc* \S
/;^f^^*7T ~ Self esteem
• •' * =' ' . Quartile 1,2,3
-5 0 5 10 15 20
I"'"'"""'™' F«.dv.lu.s |
!l?*!4lU— Hlv-^1— ' Self esteem
...•;;•/.• ' ' ' • Quartile 4
5 ° ,««»„,., 10 "
|«resldmdlvscov Fitted values |
Maternal Depression scale at delivery vs 24 month M Dl
|o V24MentMDIC.
Another Pilot Study: Maternal Child
Lung Study
• Pregnancy cohort recruited from 1986-1992
• Study of in utero/environmental tobacco smoke
exposure and respiratory outcomes
• Women enrolled before 20th EGA week
• Children followed after birth
• Measured ETV (violence) and WCST as pilot
•
Effect of Cotinine in Predicting Errors on WCST:
Stratified by Median Violence Exposure
% Errors
# Perseverative
Responses
%Perseverative
Responses
# Perseverative
Errors
% Perseverative
Errors
Cotinine Beta (Low
violence)
2.9 (p=0.6)
1.7(p=0.7)
2.0(p=0.7)
0.8 (p=0.9)
1.4(p=0.8)
Cotinine Beta (High
violence)
9.8 (p=0.07)
11.1 (p=0.007)
10.7(p=0.007)
10.7(p=0.01)
9.9 (p=0.02)
How Does Genetics play into this?
• Genetics regulates synapse formation
Pruning
n Maintenance
• Growth factors
• Protection from oxidative xenobiotics
• Nutrition
-------
(A) Astrocytes increase synapse number by secreting cholesterol bound to large
lipoprotein particles containing apolipoprotein E (apoE).
(B) These particles are internalized by neurons, leading to increased cholesterol within neuronal
membranes. It is possible that apoE also activates yet to-be-identified signaling pathways within the neurons.
(C) These changes stimulate an increase in the number and efficacy of synapses.
From: Barres: Science, Volume 294(5545).November 9, 2001.1296-1297
J
APOE and Neurodegeneration
• E4 allele associated with 2-5 fold
increased risk of AD if heterozygote
D5-17 fold increased risk if homozygote
APOE and Neurodevelopment
• Study of lead exposure and infant
development in Mexico.
• Infants enrolled at birth, cord lead levels
measured, Mothers receive calcium
supplements in RCT.
• Bayley Infant Development scales
performed at 24 months of age.
APOE and Neurodevelopment
Multivariate Analysis Beta
#APOE4 4.3(95% Cl: 0.03 - 8.5)
Study Group- subjects E4/E3. E4/E4
Referent group- subjects E3/E3, E3/E2, E2/E2
* OR adjusted for the maternal IQ, Sex, gestational
age, dietary calcium, umbilical cord blood lead
level and Maternal years of Education.
Figure 1: Smoothed Plots of MDI Score vs Umbilical Cord
Lead Levels
APOE2 or APOE3 Carrier
APOE4 Carrier
Umbilical Cord Lead Level ug/dL
VT*V-fc '.
A.*:. •;••. ..,
C2 Genotype as Modifier
of Cord Pb Effect
Transferrin C2 Wildtype
Transferrin C2 Carrier
-------
Metal Mixtures
• Just as exposure does not occur uniformly
against a given social context.
• Exposure to Neurotoxicants is mixed.
nPb
nMn
• Both have evidence of neurotoxicity.
Mexico City
Blood Mn measured on 300 infants at 1
year of age from archived samples.
Blood Pb measured at 12, 18 and 24
months
Bayley MDI at 12, 18 and 24 months.
Blood Pb and 24-month MDI Association
Varies by Blood Mn Level
Lowest 4 Quintiles of Blood Mn Highest Quintile of Blood Mn
Blood Pb (ug/dl) Blood Pb (ug/dl)
Interaction beta: -1.5, p=0.04 (N=290)
Manganese-Lead Interaction
Highest Quintile of Blood Mn x Blood Pb
Adjusted beta* p
12-month MDI
18-month MDI
24-month MDI
Repeated Measures
•Adjusted for 12-month blood Pb level, inf
-0.66 0.
-1.4 0.
-1.5 0.
-0.9 0.
28
32
34
34
ant sex, maternal IQ, maternal education
Mexico Birth cohort
• The work just reviewed led to the
establishment of a new birth cohort in
Mexico City.
• 1) R01 ES014930 Metal Mixtures and
Neurodevelopment
• 2) R01 ES013744 Stress, Lead, Iron
Deficiency and Neurodevelopment.
Mexico City Birth Cohort
• Designed to study
n Prenatal vs post-natal contributions to
development
Genetic susceptibility
n Metal mixtures
Social modifiers of toxicity
-------
Mexico City Cohort
• Long term goals
D Identify factors that increase/decrease metal
toxicity
Understand the biology of metal neurotoxicity
n Prevent toxicity
nTreat toxicity after it has occurred
Tar Creek Superfund Site
The MATCH Study
(Metals Assessment Targeting Community
Health)
"Ga-Du-Gi"- Working Together
GIGWENT
A^re in Mexico to
... •
Thanks
Element
Adrienne Ettinger
MaraTellez-Rojo
Hector Lamadrid
David Bellinger
Rosalind Wright
Howard Hu
Lourdes Schnaas
Adriana Mercado
Tar Creek
Mary Happy
MarkOsborn
Rebecca Jim
Earl Hatley
-------
Criminal Behavior as a Late
Outcome of Early Exposure to
Environmental Lead
Kim N. Dietrich, Ph.D.
Environmental Factors in Criminal
Disposition
Parental dysfunction
Community violence
Poverty
Media
Lead
Nutrition
Alcohol
Illicit Drugs
1C
Cincinnati
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Cincinnati
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Chi Id mf-.
Biological Factors in Criminal
Disposition
Functional Anatomical Characteristics of
Brain
Neurotransmitter Metabolism
Autonomic Function
Traumatic Brain Injury (Frontal Lobes)
Genetic endowment (Functional
Polymorphisms)
Criminal Behavior as an Outcome of
Childhood Lead Poisoning
Cincinnati
Cincinnati
.
t Children's
Lead Exposure and Juvenile
Delinquency: Earlier Observations
1943: Byers and Lord reported a high prevalence of behavior
problems among survivors of lead encephalopathy.
"...violent aggressive behavioral difficulties such as
attacking teachers with knives and scissors."
Byers & Lord, Am J Dis Child. 1943
Bone Lead Levels and Percentage of Children Scoring in the
Clinical Range for Aggression, Delinquency, and Attention on
the Achenbach Child Behavior Check List
Needleman.etal., JAMA, 1996.
Dr. Randolph Byers
.-..1C
Cincinoali
^Cincinnati
V Children's
Cir*ci»r»t(ti
K Cincinnati
k Children's
-------
Bone Lead Levels (ppm) in Adjudicated
Delinquents: A Case Control Study*
Cases Controls P value
n Mean(SD) n Mean (SD)
All Subjects 195 11.0(32.7) 150 1.5(32.1) 0.007
African-American 158 9.0(33.6) 51 -1.4(31.9) 0.05
White 36 20.0(27.5) 95 3.5(32.6) 0.008
'Needleman, et al. 2002, Neurotoxicol Teratol.
Other Observations: Ecological Studies
Stretesky and Lynch (2001) reported positive correlations between
homicide rates and air lead contamination levels for 3111 counties
in the US. Even after adjustment for 15 confounding variables, a
four-fold increase in homicides in the counties with the highest air
lead concentrations compared to counties with the lowest air lead
concentrations was found.
Stetesky & Lynch, Arch PediatrMolesc Med., 2001
Nevin (2000) reported a statistically significant relationship between
trends in sales of leaded gasoline and violent crime after adjustment
for such variables as unemployment rates and percent of population
in the age range where there is a higher risk for criminal behavior.
Nevin, Environ Res., 2000
.
Cincinnati
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Cincinnati
Chid n riiil i
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Limitations of Earlier Studies
• These studies suggest that exposure to
environmental lead during childhood is
associated with the development of behavioral
problems, delinquency and criminality.
• Questions remain, however, because the
majority of these studies were cross-sectional,
relied on indirect measures of lead exposure or
did not follow the children into adulthood to
examine the relationship of lead exposure with
persistent criminality.
"Cincinnati FHBlKr,sr«,: f
The Cincinnati Lead Study of Juvenile
Delinquency and Adult Criminality
Cincinnati Lead Study catchment are;
Cincinnati
ft
Children's
The Cincinnati Lead Study
A prospective, longitudinal study initiated in
1979 that is examining the early and late effects
of childhood lead exposure on growth and
development with a particular emphasis on
neurobehavioral outcomes.
The Cincinnati Lead Study has collected data on
exposure (blood lead concentrations),
neurobehavior, child health, and
sociodemographic variables on a quarterly to
yearly basis since its inception.
—It
Cincinnati 511?"™,.™ Mb. Children's
Blood Lead Concentrations in the Cincinnati Lead Study
ch, et al. Pediatrics, 1993.
Cir*cinrK(li
ft
Cincintiali
Chihtn-n's
-------
Association of Blood Lead Levels and Self-Reported
Delinquency in 16 Year-Old Adolescents in the
Cincinnati Lead Study
Prenatal PbB
Average Childhood PbB
78 Month PbB
o
Low est Low Medium
Blood Lead Level
Dietrich, et al. 2001, Neurotoxicol Teratol.
High
i'X
CindmidTi
Children-.
Cincinnati Lead Study Cohort as Adults
(N = 250)
Characteristic
Subject Characteristics
-....VST
Cincinnati
No. (°/y/Mean(SD)
225 (90 0%)
22.5(1.5)
29(11 6%)
Children's
Cincinnati Lead Study Cohort as Adults
(N = 250)
Maternal Characteristics
Age at delivery (years)
Maternal IQ (points)
High School graduate
HOME Inventory at age 3 (points)
History of arrest (yes)
Marital Status
Cincinnati
No. (°/
-------
Blood Lead Concentrations and Arrests for
Violent Offenses in the Cincinnati Lead Study
Mechanisms: How Does Lead Increase
Antisocial Behavior?
6 9 12 15
Six-year Blood Lead Concentration (ug/dL)
Direct route: Lead affects brain systems that regulate social-
emotional functioning, Including neurotransmltter metabolism
and function, and neural growth, survival and differentiation In
critical areas such as prefrontal cortex Gene-environment
interactions may also play a role.
Indirect route: Early lead exposure Is associated with higher
rates of school failure and reading disabilities. Students who do
poorly In school are more likely to engage In delinquent and
criminal activities.
.
Cincinnati
C Cincinnati
S Children's
-....VST
Cincinnati
/» Chid n riiil i
-------
Thn Costs nf Sprawl
i ,1.:' :^ L. ' i'
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ipact development patterns prodi*
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3,000
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600 |
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300
200
100
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Year
Urban Sprawl
and Public Health
-------
-------
-
JAMA"
s to Children Walking to or From School-United States, 2004
n [»rt of *> octa* Htiltfn th»1
-------
-------
JL
Well-Connected
Street Network
Typical Subdivision
Cu I-de-Sacs
-------
\\.iik-otul.i (II) Sdionl H.ins HiU".
si-ss
7
-------
Voters say no to 'mega-campus'
STOP
$54 MILLION
MEGA-CAMPUS!
VOTE FOR THE
iBORHOOD]
1^ '•<>,:: g
Challengers overwhelm
incumbents to w in seats on
Pottsiwn School Board
KIUVIIWN - Votan *
-------
Renovate or Replace?,
Travel end Environmental
ImpBcations of School Slug
Expert tests walking routes
-------
For more information..
- My Contact information:
- Tim Torma
- torma.tim@epa.gov
- 202-566-2864
- www.epa.gov/smartgrowth/schools
10
-------
Environews Spheres of Influence
Community Impacts of Goods Movement
VOLUME 1161 NUMBER 2 I February 2008 • Environmental Health Perspectives
-------
Spheres of Influence Global Trade Comes Home
For many U.S. residents, 2007 was a year of heightened
awareness of some of the problems of global trade.
Extensive recalls of melamine-tainted pet food in the spring
followed by even larger toy recalls in the summer and fall raised
consumer concerns about how the United States can ensure the
safety of products shipped in from overseas. The Salt Lake Tribune
and the Wall Street Journal detailed injuries and illnesses threaten-
ing the health of Chinese workers making products for export to
the United States. And on 15 December 2007, a New York Times
feature detailed the practice of farming fish in toxic Chinese waters
for export to the United States and other countries.
While these news stories demonstrate some of the pitfalls of
globalization, much less attention has focused on air pollution and
other community-level impacts in the United States, as toys, elec-
tronics, food, and other imports travel through ports, then to
trucks, trains, warehouses, and stores in a complex system called
"goods movement." Along the route, residents are exposed to diesel
exhaust and other vehicle emissions, noise from truck-congested
roads, bright lights from round-the-clock operations, and other
potential health threats.
Transportation experts refer to these impacts simply as "external-
ities" of transport, but to community residents they can directly
harm the quality of daily life. As ports and goods movement activity
expands throughout the United States, a major challenge is how to
make its health and community impacts a more central part of policy
discussions.
Economic Benefits, Community Costs
Economic development advocates call the side-by-side ports of Los
Angeles and Long Beach Southern California's "economic engine."
Combined, they handle the most containers of any U.S. port.
With more than 40% of all imports for the entire United States
coming through the Los Angeles/Long Beach port complex,
according to the U.S. Department of Transportation, the ports are
critical to the national economy. A March 2007 national economic
impact study by the twin ports reported that imports coming
Children play soccer next to the TraPac terminal at the Port of Los Angeles,
Wilmington, California.
A 79
-------
Spheres of Influence Global Trade Comes Home
through the complex generated jobs, income,
and tax revenue in every state of the nation.
While recognizing the economic impor-
tance of international trade, the U.S.
Environmental Protection Agency (EPA) has
called the movement of freight a "public
health concern at the national, regional and
community level." In a 22 August 2007
Federal Register announcement of a meeting
of its National Environmental Justice
Advisory Council (NEJAC), the EPA also
described mounting evidence that local com-
munities adjacent to ports and heavily traf-
ficked goods movement corridors are the
most significantly impacted by the goods
movement system.
The ports of Los Angeles/Long Beach
combined contribute more than 20% of
Southern California's diesel particulate pollu-
tion and are the single largest source of pollu-
tion in Southern California, according to the
South Coast Air Quality Management
District (AQMD), the region's air quality reg-
ulatory agency. The California Air Resources
Board (GARB), in its 2006 Emission Reduc-
tion Plan for Ports and Goods Movement, cal-
culated that in California alone there are
2,400 premature heart-related deaths related
to port and goods movement pollution,
62,000 cases of asthma symptoms, and more
than 1 million respiratory-related school
absences every year. Nationwide, reports
James Corbett of the University of Delaware
and colleagues in the 15 December 2007 issue
of Environmental Science & Technology, an
estimated 60,000 lives are lost prematurely
every year due to ship emissions, which are
virtually unregulated.
Recent research findings about living close
to traffic emissions add to concerns. A study
by investigators at the University of Southern
California (USC), published 17 February
2007 in The Lancet, showed that children liv-
ing near freeway traffic had substantial deficits
in lung function development between the
ages of 10 and 18 years, compared with chil-
dren living farther away. "Since lung develop-
ment is nearly complete by age eighteen," says
lead author W. James Gauderman, "an indi-
vidual with a deficit at this time will probably
continue to have less than healthy lung func-
tion for the remainder of his or her life."
Other studies published in the February
2003 and September 2005 issues of EHP
linked traffic exposure to increased risk for
low birth weight and premature birth. A new
study published 6 December 2007 in the
New England Journal of Medicine showed that
adults with asthma who spent just 2 hours
walking on a street with heavy diesel traffic
suffered acute transient effects on their lung
function along with an increase in biomarkers
that indicate lung and airway inflammation.
In addition, research by the EPA-funded
Southern California Particle Center at the
University of California, Los Angeles, pub-
lished in the April 2003 issue of EHP,
demonstrated that ultrafine particles from
incomplete combustion of engine fuels and
lubricating oils can bypass the body's defense
mechanisms, gain entry to cells and tissues,
and alter or disrupt normal cellular function.
Regulation to Date
In 2005, GARB issued guidelines that recom-
mend avoiding construction of new schools
and homes within a mile of a railyard or
500 feet of a busy highway. A few years earlier,
California legislators, citing health effects
research findings, passed SB 352, a law pro-
hibiting building new schools within 500 feet
of a busy road or freeway. But the 2003 law
permits several loopholes, such as allowing a
school district to show that it is able to mitigate
traffic emissions so that pupils and staff will
suffer no significant health risk. The law also
requires that a school district verify that any
railyard within a quarter mile of a new school
will not present a public health threat. Some
school districts, in the scramble to build new
facilities, are continuing to site new schools
near freeways and rail operations.
Conversely, railyards and freeways also
continue to be proposed in close proximity to
schools and homes, such as a proposed truck
expressway to speed trucks away from the
Southern California ports, which would pass
within 100 feet of homes and 700 feet of a
local school. The draft environmental impact
statement (EIS) for the project, issued in
August 2007 by the California Department of
Transportation (Caltrans) acknowledges the
scientific research: "Some recent studies have
reported that proximity to roadways is related
to adverse health outcomes—particularly res-
piratory problems." But the EIS goes on to
say that using these studies to determine if
there will be adverse impacts from the truck
expressway project is premature.
According to Ron Kosinski, deputy dis-
trict director for the Caltrans district covering
Los Angeles County, the Federal Highway
Administration (FHWA) is delaying any pol-
icy decisions related to health effects from
proximity to traffic until the conclusion of a
review of all the studies by the Health Effects
Institute—a report that is not expected for
several years. FHWA spokesman Doug
Hecox says, "[The agency is] not suggesting
that nothing should be done. But there are
no conclusive studies right now drawing a
direct relationship between the number of
trucks on a road and the percent of impair-
ment of an affected child."
Environmental, community, and public
health groups have long pressured Los Angeles
and Long Beach port authorities to take
action on port pollution. In 2006, an historic
agreement called the Clean Air Action Plan
(CAAP) was signed, vowing that the ports
would reduce air pollution by 45% within the
next 5 years. However, some community and
environmental groups are concerned that the
deadlines set in the CAAP are slipping.
Port of Los Angeles executive director
Geraldine Knatz responds that the CAAP "is a
five-year process that requires major invest-
ment in construction and new equipment, and
in the interim, cargo movement through our
ports continues." Knatz also points to a new
program to reduce port-related truck emis-
sions by 80% by 2012—a $2 billion initiative
that she says "cannot simply happen
overnight." In December 2007, both ports
adopted container fees to fund the replace-
ment of 17,000 polluting big-rig trucks with
new models that meet tighter EPA diesel emis-
sion standards.
At the state level, GARB issued new rules
in December 2007 that would require ships
to plug in to electricity rather than using
diesel auxiliary engines when docked in the
harbor and that would require stricter emis-
sions standards for trucks frequenting ports
and railyards. The South Coast AQMD has
long championed stricter controls on ports
and rail operations to protect public health, as
well as environmental justice considerations.
In 2006 the agency issued rules to reduce pol-
lution from idling locomotives in railyards,
but railroad companies sued to block them.
In 2007 a Los Angeles-based U.S. District
Court judge struck down the agency's rules,
arguing that it lacked authority to adopt
them; the agency is appealing the decision.
According to the South Coast AQMD,
emissions from ships are also underregulated,
with no significant international or federal
emission control regulations. In 2004, the
EPA announced plans to put in place new
standards for ships and locomotives. On
15 January 2008, the Greenwire news service
reported these standards were under review at
the White House Office of Management and
Budget, which must approve them before the
EPA can sign off on them.
Increased Trade Expected
The health and environmental justice impacts
of port, rail, and trucking pollution are not
limited to California. In South Carolina, for
example, environmental groups and home-
owners are troubled by anticipated impacts of
a proposed terminal expansion at the old
Charleston Navy Base, which the South
Carolina Coastal Conservation League says
will triple the container volume through
Charleston and generate thousands more
truck trips a day through a low-income black
neighborhood. "An access road and off-ramp
will go right through our Rosemont commu-
nity as trucks leave the port terminal for the
A 80
VOLUME 1161 NUMBER 2 I February 2008 • Environmental Health Perspectives
-------
Spheres of Influence Global Trade Comes Home
nearby interstate highway," New Rosemont
Neighborhood Association president Nancy
Button told participants of a recent commu-
nity-academic conference on port health
impacts held in Los Angeles.
According to The Journal of Commerce
Online (JoC), a news magazine covering inter-
national trade and goods movement, many
U.S. ports are expanding in hopes of capitaliz-
ing on rising international trade volumes.
Historically, says maritime industry economist
Bill Ralph, as quoted in the 16 January 2008
JoC, international container trade in the
United States has an annual growth of about
7%. In 2006, U.S. containerized imports grew
by 11%. But in 2007, says Ralph, they
increased by only 3%, due to a slowdown in
the housing and auto markets. Economist
Walter Kemmsies, quoted 2 days earlier in the
JoC, predicts that U.S. container trade will
return to its normal 7% annual growth within
the next 2 years and continue to grow steadi-
ly—even faster if the United States enters into
more free trade agreements.
The EPA Office of Environmental Justice
(OEJ) has taken note of the growth trends
and the rising environmental health concerns
about port and goods movement expansion.
In August 2007, acting OEJ director Charles
Lee appointed a new working group to study
the impacts of ports and goods movement
through an "environmental justice lens,"
with a report expected in June 2008. Land
use decision making will be 1 element in the
report, along with community participation,
regulatory mechanisms, innovative technolo-
gies, and more.
Projected increases in foreign trade, along
with many states' planned expansion of high-
ways, rail facilities, and ports to handle Asian
imports, cause concern about increased air
pollution if regulations to reduce emissions
do not keep pace with trade growth. In the
22 August 2007 Federal Register, the EPA
noted that the anticipated increase in trade
will have air quality impacts, and the agency
threw out a challenge to the ports and com-
panies involved in goods movement: "It is
becoming increasingly important that these
entities operate sustainably, i.e., economically
viable, environmentally and socially responsi-
ble, safe and secure."
Community Response
As this global goods movement system
expands, communities across North America
are now recognizing that they are facing simi-
lar circumstances and common conflicts. And
they are banding together, in small and large
coalitions, to address the impacts.
In the 1990s, just a few groups such as the
Sierra Club, the Environmental Health Coali-
tion, the Center for Community Action and
Environmental Justice, and homeowners near
the ports were focused on the effects of the global
supply chain. But 2001 turned out to be a
watershed year. That year, the Natural Resources
Defense Council, the Coalition for Clean Air,
Communities for a Better Environment, and
2 harbor-based homeowner's associations filed a
lawsuit challenging the Port of Los Angeles's
environmental review of planned construction
for a major shipping terminal. Two years later
they won a $50 million landmark settlement
from the city requiring environmental mitiga-
tions, such as the "plug in" rule issued by GARB
in December. A new era had begun—one that
started to shift public attention from the role of
international trade simply as the region's major
economic engine to the potential perils of
uncontrolled goods movement expansion.
That same year, the NIEHS-funded
Southern California Environmental Health
Sciences Center, based at USC, held a town
meeting to share its research findings with
community groups, residents, workers, and
policy makers. In turn, scientists heard the
emerging concerns of residents about diesel
emissions near the ports, railyards, and ware-
houses. Research findings on the health
impacts of air pollution soon began to find
their way into policy debates on goods move-
ment and port expansion.
Over the next 5 years, multiple partner-
ships started to come together to specifically
address issues of ports and goods movement
in California. Among the collaborative efforts
active today are the Ditching Dirty Diesel
Collaborative based in Oakland, aimed at
developing a regional strategy to reduce diesel
emissions; the Trade, Health & Environment
(THE) Impact Project, a community-
academic collaborative aimed at elevating
community voices in the goods movement
policy debate and using science-based infor-
mation to inform public policy; the Port
Work Group of Green LA, which aims to
ensure that the Port of Los Angeles becomes
truly green, with the support of the city's
mayor; and a broad-based coalition aimed at
improving wages and working conditions
(including less-polluting vehicles) for port
truck drivers.
Elsewhere, residents in a neighborhood
near the Port of Seattle have been counting
big-rig trucks parked overnight in their com-
munity in an effort to keep port-related pollu-
tion, safety hazards, and blight out of their
neighborhoods. In Arizona, a school superin-
tendent has asked officials not to enact zoning
changes that would allow construction of a
major intermodal facility (a railyard at which
cargo is transferred between trucks and trains)
across the street from a local elementary
school. And on Long Island, residents are ask-
ing the state of New York to reconsider its
plans to build an intermodal facility near resi-
dential communities and a wildlife preserve.
Tools for Action
Many groups impacted by ports and goods
movement came together in late 2007 at
Moving Forward, the first North American
community-oriented gathering on this topic,
which was organized by THE Impact Project
and cosponsored by private groups along with
NIEHS- and EPA-ftinded centers.
Participants shared information on cur-
rent health research related to goods move-
ment, community concerns about health
impacts, future goods movement expansion
projects (such as plans to deepen the harbor at
the Port of Savannah, Georgia, to handle larg-
er ships carrying twice as many containers),
and community efforts to effect change.
Presenters described tools for action, such as
methods for mapping goods movement activ-
ities in communities; understanding who the
key goods movement stakeholders and deci-
sion makers are; ways to incorporate credible,
current scientific research findings into educa-
tional and policy efforts; and new methods
for developing health impact assessments.
Eric Kirkendall from Kansas was struck
by the commonalities at the conference. Back
home, he had formed the Johnson County
Intermodal Coalition in response to proposals
to build an intermodal railyard near the small
town of Gardner and surround his 4-acre
homestead on 3 sides with 12-acre warehouses.
Kirkendall says, "We sometimes feel alone in
Kansas. But by the end of the conference I
understood that we are not alone. We have
much to share with, and learn from, other
groups with similar challenges, as well as from
scientists and policy makers."
Some attendees thought more attention
should be focused on American consumer
habits, a point echoed by Rev. Peter Laarman,
executive director of Progressive Christians
Uniting. He urges a closer look at the hidden
costs of imports. "Americans think of them-
selves as consumers rather than as citizens," he
says. "We don't care, for example, if Chinese
workers toil in factories with no safety regula-
tions, or if residents in communities near our
ports have to breathe dirtier air. What we care
about is 'How much do I have to pay for an
iPod?' and 'Where can I buy this doll for
under ten dollars?'"
By their very nature, the ports and goods
movement debates faced by community
groups throughout North America can help to
inform future discussions about consumerism
and globalization. As far as health effects go,
however, research findings and community
experience are strongly suggesting that global
trade, while an apparent boon to our economy,
will continue to pose a serious threat to our
population's environmental health unless pro-
tective and collective action is taken, and soon.
Andrea Hricko
Environmental Health Perspectives • VOLUME 116 I NUMBER 2 I February 2008
A81
-------
T
THE NATIONAL !\
CHILDREN'S
STUDY
MARION J. BALSAM M.D.
Research Partnerships Program Director
National Children's Study
National Institute of Child Health and Human Development/NIH/DHHS
THE NATIONAL CHILDREN'S STUDY:
ADJUNCT STUDIES
2007 Children's Environmental Health
W IV» U |J • C I rt
October 12, 2007
*
US Department of Health
and Human Seivices
US Environmental
Protection A9ency
-------
Authorized in 'The Children's Health Act of 2000':
study effects of the environment on child health and
development
Environment broadly defined:
chemical, biological, physical, psychosocial-cultural
Gene-environment interaction and gene expression
Largest/longest such study ever conducted in the U.S.
Lpngitudinal study of 100,000 children, from before
birth (even before conception) through age 21
Representative sample of children across the U.S.
Power to study important but uncommon outcomes 0
National resource for future research
-------
Identify environmental effects on children:
- harmful, harmless, and helpful
- in the context of gene-environment interaction
Identify preventable causes of important
health-related conditions in children
Provide evidence-based data to guide decisions
regarding children's healthcare and health policy s°
-------
Program Office (PO) at NICHD - NCS Director,
scientists, administrative staff
Interagency Coordinating Committee - NICHD, CDC,
EPA, NIEHS
Chartered Advisory Committee
Federal Consortium: key government agency reps
Steering Committee - Study Center Pis, federal
scientists and community representatives
Coordinating Center - Data management/coordination
Study Centers - 7 Vanguard Centers & 22 new Cente^
Study Assembly - 4500 interested scientists & othei
-------
National Children's Study Locations
t
THI NATIONAL V\
CHILDREN'S
BTUDT
®
®
®
®
®
®
®
®
®
®
®
®
®
®
®
®
®
Map Legend
% 2007 Locations
Vanguard Locations
® 2008-2010 Location*
reJH^
®
®
-------
Priority
Exposures
Physical
Environment
Chemical
Exposures
Biologic
Environment
Genetics
Psychosocial-
cultural Milieu
Examples
Housing quality,
neighborhood
Pesticides,
phthalates, heavy
metals
Infectious agents,
endotoxins, diet
Interaction between
environmental
factors and genes
Families, SES,
institutions, social
networks
Priority Health
Outcomes
Pregnancy
Outcomes
Neurodevelopment
& Behavior
Injury
Asthma
Obesity & Physical
Development
Examples
Preterm, Birth
defects
Autism,
schizophrenia,
learning
disabilities
Head trauma,
Injuries
requiring
hospitalizations
Asthma
incidence and
exacerbation
Obesity,
Diabetes,
altered puber
-------
Leveraging the
National Children's Study
The Research Plan or Protocol...
The potential links between
exposure & outcome measures.,
The ongoing research findings
as the Study progresses...
will spark ideas for
further research
leveraging the core study
->adjunct study proposals
-------
• Involve a subset of the NCS cohort
• Modular, focused studies utilizing NCS
infrastructure: participants, and/or
bio-specimens, and/or environmental
samples.
Initiated by: government scientists,
Study Center scientists, independent
investigators, research advocates,
industry...
-------
Focus
•a unique research interest/capability
or
•a specific public health or community
concern
Utilize, complement, leverage the core
protocol for mutual benefit
"Outside' (not core-NCS) funding oNjr"
-------
• Scientific merit
• Public health importance: potential
contribution to health care or policy
•AFit' with the NCS (priority exposure
or outcome, sampling, tools, timing...)
•Appropriate use of bio-specimens and
environmental samples
-------
Burden on participants (time,
discomfort...)
Burden on the Study infrastructure
(logistics...)
Human Subjects issues: ethical &
legal considerations
Peer review, IRB review, funding
-------
Brief electronic Preliminary Application
The Full Application is provided after NCS
approval of the Preliminary Application
Iterative process to facilitate timely
review of proposals: Program Office, ICC,
Steering Committee, Sample Oversight
Group...
-------
"Partnerships' with government agencies
(e.g. intramural scientists and funding;
RFAs to extramural scientists...)
Government grants (e.g. R-01...)
Public-private partnerships: industry,
foundations, academia, research advocacy
groups, etc.
-------
July 2008 to July 2009: VC pilot year
July 2009: Enrollment begins at
Vanguard and new Study Centers for
the Afull Study'
Adjunct Study proposals for pre-
conception, pregnancy, delivery,
newborn and early infancy periods
could be submitted soon to commence
-------
• Opportunities will continuously arise for
additional research by leveraging the NCS
Opportunities exist for public-public
(other government agencies) and public-
private partnerships
• Adjunct studies will broaden and enhance
the NCS contribution to children's
environmental health
• On the NCS website:
• "Adjunct Study Overview'
•Application for adjunct study proposal
-------
Marion J. Balsam M.D.
Research Partnerships Program Director
The National Children's Study
/w.N ilChild ly-gc
cs@r il.nih.
Adjunct Studies:
NCSAdjunctStudies@mail.nih.gov
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Tools for Recovery and
Communicating Risks After
Hurricane Katrina
Objectives of Today's Panel
Describe the collaborative PEHSU
response to Hurricanes Katrina and Rita
(Debra Cherry, MD)
Experience and feedback from a Gulf
Coast pediatrician at Ground Zero (Scott
Needle, MD)
New tool: The NIEHS Hurricane Response
Portal (Marie Lynn Miranda, PhD)
Discussion
Disaster Strikes: Aug 29, 2005
Over 354,000 Gulf Coast homes
destroyed
Over 200 sewage treatment plants and
140 oil and gas platforms damaged
Rampant mold growth
Mountains of debris
Widespread demolition/reconstruction
projects
Residents in temporary housing
Tyler: The closest PEHSU
Tyler, TX to
New Orleans:
424 miles
In Katrina's Wake...
"This is the mother of all multidisciplinary
problems"-John McLachlan, Tulane/Xavier
Research Scientist*
"The public health community must articulate
key health issues, keep the message simple and
focused, and develop effective strategies to
provide targeted timely results" - Kellogg
Schwab, Johns Hopkins Bloomberg School of
Public Health*
*Lessons Learned, In Katrina's Wake, EHP 114
(1): Jan 2006, pg A39
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Joint Documents and
Recommendations
NYC, Atlanta, and Tyler PEHSUs
- Clinician recommendations for return of children to
previously flooded and/or hurricane impacted areas
EPA: Siobhan McNally (Boston PSR), Martha
Berger, Michael Shannon
- Tip Sheets for Parents - Mold, sludge
- Environmental Questionnaire for Clinicians
More Recently - Poor indoor air quality in FEMA
trailers
- Formaldehyde fact sheet
Sample Call: Formaldehyde,
July 2007
A mother called
SWCPEH regarding
her 6 y/o daughter
with a nasal polyp
and nosebleeds
several times per
month. She and her
daughter have been
living in a FEMA
trailer in the New Orleans area since Katrina (almost 2
years as of July). The girl has no known allergies, and
the problems started in the last year. Mom wants to
know if this could be related to formaldehyde.
"My home"; www.fematrailersong.com
Sample Call: Sludge, Sep 2005
A mother of three children,
ages 8, 4, and 3 months,
called about moving back
to her home that had
standing water for 3
weeks and sludge
contaminants from an oil
refinery spill. The refinery
offered to remove the soil
from her yard and sludge
from her home.
Photo: Clip art from PowerPoint
Summary: SWCPEH/PEHSU
Network Hurricane Response
Prepared guidelines for returning children
to previously flooded areas
Prepared fact sheets and questionnaires
in conjunction with EPA, PSR
Answered calls from concerned parents
-------
Children's Environmental Health Initiative
A research, education, and outreach
program committed to fostering
environments where all children can
prosper.
12 October 2007
New Orleans: Before and After Hurricane Katrina
Regional Overview
Before
After
Extent of Flooding
Industrial Canal Levee Breach
Lower 9th Ward Pre Katrina
Lower 9th Ward September 1st, 2005
-
Lower 9th Ward December 14th, 2005
, —-=•-=•«•
-------
Key Health Consequence Questions
NIEHS Response: Web Portal
• Mold and respiratory health
• Contaminant transport
• Solid waste management
• Mental health
•Build and maintain extensive data archive designed
to investigate environmental health consequences of
the hurricanes
•Provide a collaborative workspace for analysis of
georeferenced data
•Provide a Gulf Coast resource to support
environmental health research more broadly
Collaborative Team
•NIEHS
•Columbia University (ClESIN)
•University of Kentucky
•Research Triangle Institute
•San Diego State University
• University of California, San Diego
•Duke University
NIEHS Hurricane Response Web Portal
i. 0
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Analysis Tools
Models for Customizing Research Environments
project-
based
field of
research
additional
approaches
Project Based Research Environment
Custom Reports
HEALReport
Defining the Geographic Scope
Acknowledgements
http://www.rS*hs»nlh,gov
hurricanegis@niehs.nih.gov
-------
Children's Protection in the Aftermath of „
Natural Disaster: Tools for Recovery and
Communicating Risks
Tales from Ground Zero:
Hurricane Katrina and Pediatric
Environmental Health in Coastal
Mississippi
Scott Needle, MD, FAAP
October 12, 2007
-------
Risks after Katrina:
and in-betweens
Debris
I Mold
Gastrointestinal illness
> "Katrina Cough"
• "Katrina Brain"
1 Psychological trauma and the honeymoon
period
Lessons Learned
lurring the line b/t "public" and "private"
Shortage of resources in disaster area
Communication is the priority
Keep eyes and ears open
Flexibility and ingenuity
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